# https://retevmo.lilly.com/ llms-full.txt ## Retevmo Cancer Treatment [Skip to main content](https://retevmo.lilly.com/#maincontent) Information To continue using a Savings Card in 2025, eligible patients can download now under the [Savings & Support Page](https://retevmo.lilly.com/savings-support). ## **Retevmo** ® Now in tablet form with four dose strengths. [Learn More](https://retevmo.lilly.com/assets/pdf/retevmo-dtc-digital-patient-flyer.pdf) ![Reimagine tomorrow with Retevmo for Ret-positive nsclc, thyroid and other cancers.](https://retevmo.lilly.com/_nuxt/img/transparency.6ce42a6.png) Scroll Down Down ![Reimagine tomorrow with Retevmo. Retevmo is an oral targeted therapy you can take at home](https://retevmo.lilly.com/assets/img/dual_indication_campaign_dtc.jpg) # Retevmo is a targeted therapy you can take at home With Retevmo, it's time to reimagine tomorrow The first FDA-approved treatment for people with _RET_-positive advanced non-small cell lung cancer (NSCLC), thyroid cancers, and certain other cancers. Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. RET=rearranged during transfection. How can Retevmo help? I have [_RET_-positive advanced NSCLC](https://retevmo.lilly.com/about-mnsclc) I have [_RET_-positive advanced thyroid cancer](https://retevmo.lilly.com/about-mtc) I have a different type of [_RET_-positive advanced cancer](https://retevmo.lilly.com/other-cancers) I'm starting on Retevmo. [How do I take it?](https://retevmo.lilly.com/taking-retevmo) ![Savings and support for Retevmo](https://retevmo.lilly.com/assets/img/home-savings-support-cta-hero.png) ## Savings and Support Resources We’re here to help during your or your loved one’s treatment. Discover the support, savings, and resources that may be available to you with [Retevmo Savings and Support](https://retevmo.lilly.com/savings-support). [Discover Retevmo Savings and Support](https://retevmo.lilly.com/savings-support) Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo Resources https://retevmo.lilly.com/about-mnsclchttps://retevmo.lilly.com/about-mtchttps://retevmo.lilly.com/hcphttps://retevmo.lilly.com/how-it-workshttps://retevmo.lilly.com/other-cancershttps://retevmo.lilly.com/patient-storieshttps://retevmo.lilly.com/savings-supporthttps://retevmo.lilly.com/sitemaphttps://retevmo.lilly.com/taking-retevmohttps://retevmo.lilly.com/what-is-rethttps://retevmo.lilly.com/hcp/about-rethttps://retevmo.lilly.com/hcp/dosinghttps://retevmo.lilly.com/hcp/safetyhttps://retevmo.lilly.com/hcp/savings-supporthttps://retevmo.lilly.com/hcp/testinghttps://retevmo.lilly.com/hcp/efficacy/libretto-001https://retevmo.lilly.com/hcp/efficacy/libretto-431https://retevmo.lilly.com/hcp/efficacy/libretto-531https://retevmo.lilly.com/ ## Retevmo for NSCLC [Skip to main content](https://retevmo.lilly.com/about-mnsclc#maincontent) ![Learn more about Retevmo in NSCLC](https://retevmo.lilly.com/_nuxt/img/transparency.6ce42a6.png) Scroll Down Down ![Learn more about Retevmo in NSCLC](https://retevmo.lilly.com/assets/img/about-mnsclc-hero.jpg) # What is advanced non-small cell lung cancer (NSCLC)? Lung cancer is a cancer that starts in your lungs. There are 2 main types of lung cancer: NSCLC and small cell lung cancer. About 85% of people with lung cancer have NSCLC. Lung cancer may spread to other parts of the body, including bones, adrenal glands, the brain, and the liver. People with lung cancer whose cancer cells have spread to these places likely have advanced or metastatic cancer. Advanced NSCLC can be driven by a gene in your body. One of those genes is _RET_. [Talk to your doctor](https://retevmo.lilly.com/what-is-ret?section=talk-to-doctor) to see if your cancer is _RET_-positive. RET=rearranged during transfection. Retevmo is available for _RET_-positive advanced NSCLC ## Retevmo may help by targeting what is driving your _RET_-positive advanced NSCLC Retevmo was studied in the largest clinical trial of people with _RET_-positive cancers. The trial included people with advanced NSCLC, and 316 had tumors that were eligible to be evaluated for shrinkage. The trial evaluated how many people responded to treatment, which means their tumors either shrank or disappeared completely, and how long the response lasted. Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. ## **Retevmo was shown to shrink tumors in the majority of people with _RET_-positive advanced NSCLC** ![84% ORR for NSCLC](https://retevmo.lilly.com/assets/img/84.png) **of the 69 people who had never received any cancer treatment had an objective response, meaning their tumors shrank by 30% or more** - **Responses lasted a median\* of 20.2 months** ![61% ORR for NSClC](https://retevmo.lilly.com/assets/img/61.png) **of the 247 people who had prior cancer treatment† had an objective response, meaning their tumors shrank by 30% or more** - **Responses lasted a median\* of 28.6 months** \*Median is the middle number in a range of numbers. †Platinum-based chemotherapy; some had also received other therapies. **SELECT SAFETY INFORMATION** **RETEVMO may cause serious side effects, including:** **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your doctor if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain ## **In the trial, Retevmo reduced the size of tumors in the brain in people with advanced _RET_-positive NSCLC** ![4 of the 5](https://retevmo.lilly.com/assets/img/4-of-the-5.png) **people who had never received any cancer treatment, and whose advanced NSCLC had spread to their brain, saw their brain tumors either shrink by at least 30% or disappear completely** - **38% of responders had a response that lasted at least 12 months** ![14 of the 16](https://retevmo.lilly.com/assets/img/14-of-the-16.png) **people who received prior cancer treatment,† and whose advanced NSCLC had spread to their brain, saw their brain tumors either shrink by at least 30% or disappear completely** - **39% of responders had a response that lasted at least 12 months** †Platinum-based chemotherapy; some had also received other therapies. Learn how to take Retevmo [Retevmo dosing](https://retevmo.lilly.com/taking-retevmo) Read more about what could be driving your cancer [What is _RET_?](https://retevmo.lilly.com/what-is-ret?section=what-is-ret) Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo for Thyroid Cancer [Skip to main content](https://retevmo.lilly.com/about-mtc#maincontent) ![Learn more about Retevmo in MTC](https://retevmo.lilly.com/_nuxt/img/transparency.6ce42a6.png) Scroll Down Down ![Learn more about Retevmo in MTC](https://retevmo.lilly.com/assets/img/about-mtc-hero.jpg) # What is advanced thyroid cancer? Thyroid cancer is a cancer that starts in your thyroid gland. The most common types of thyroid cancer are papillary and follicular. Other types include Hurthle, medullary, and anaplastic. Thyroid cancer may spread or metastasize to other parts of the body, including lungs, bones, and occasionally the brain. People with thyroid cancer who have cancer cells in these parts of the body likely have advanced or metastatic cancer. Advanced thyroid cancer can be driven by a gene in your body. One of those genes is _RET_. [Talk to your doctor](https://retevmo.lilly.com/what-is-ret?section=talk-to-doctor) to see if your cancer is _RET_-positive. RET=rearranged during transfection. Retevmo is available for _RET_-positive advanced thyroid cancer ## Retevmo may help by targeting what is driving your _RET_-positive advanced thyroid cancer Retevmo was studied in the largest clinical trial of people 12 years of age and older with _RET_-positive cancers. The trial included people with advanced thyroid cancer (including medullary, papillary, poorly differentiated, anaplastic, and Hurthle cell), and had tumors that were eligible to be evaluated for shrinkage. The trial evaluated how many people responded to treatment, which means their tumors either shrank or disappeared completely, and how long the response lasted. Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. ## **Retevmo has been shown to shrink tumors in the majority of people with _RET_-positive advanced medullary thyroid cancer (MTC)** ![76% in red text](https://retevmo.lilly.com/assets/img/76.png) **of the 55 people who had prior cancer treatments\* had an objective response, meaning their tumors shrank by 30% or more** - **Responses lasted a median† of 45.3 months** ![81% in red text](https://retevmo.lilly.com/assets/img/81.png) **of the 88 people who had not received certain standards of care‡ had an objective response** - **Median† length of response has not yet been reached, as the trial is ongoing** \*Cabozantinib and/or vandetanib. †Median is the middle number in a set of numbers. ‡Not treated with cabozantinib and/or vandetanib. **SELECT SAFETY INFORMATION** **RETEVMO may cause serious side effects, including:** **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your doctor right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) ## **Retevmo has been shown to shrink tumors in the majority of people with other _RET_-positive advanced thyroid cancers** ![85% in green text](https://retevmo.lilly.com/assets/img/85.png) **of the 41 people who had prior cancer treatments§ had an objective response** - **Responses lasted a median† of 26.7 months** ![96% in green text](https://retevmo.lilly.com/assets/img/96.png) **of the 24 people who had not received certain standards of care\|\| had an objective response** - **Median† length of response has not yet been reached, as the trial is ongoing** †Median is the middle number in a set of numbers. §Radioactive iodine in addition to other systemic therapy. \|\|Not treated with systemic therapies other than radioactive iodine. ## **Retevmo was studied in a clinical trial of 291 people 12 years of age and older, with advanced or metastatic _RET_-driven medullary thyroid cancer (MTC).** The study compared Retevmo to cabozantinib or vandetanib and measured how long patients lived without their cancer getting worse. ![14% in red text](https://retevmo.lilly.com/assets/img/14.png) **of the 193 patients who received Retevmo saw their cancers get worse (also called “disease progression”).** ![34% in red text](https://retevmo.lilly.com/assets/img/34.png) **of the 98 patients who received cabozantinib or vandetanib saw their cancers get worse (also called “disease progression”).** Objective response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy. Duration of Response (DoR) is the length of time that a patient continues to respond to treatment without the cancer growing or spreading. **SELECT SAFETY INFORMATION** **RETEVMO may cause serious side effects, including:** **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your doctor if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech Learn how to take Retevmo [Retevmo dosing](https://retevmo.lilly.com/taking-retevmo) Read more about what could be driving your cancer [What is _RET_?](https://retevmo.lilly.com/what-is-ret?section=what-is-ret) Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo Oncology Treatment [Skip to main content](https://retevmo.lilly.com/hcp#maincontent) Information To continue using a Savings Card in 2025, eligible patients can download now under the [Savings & Support Page](https://retevmo.lilly.com/hcp/savings-support). ## **Retevmo** ® Now in Tablet Form with Four Dose Strengths [Learn More](https://retevmo.lilly.com/assets/pdf/retevmo-hcp-tablet-inform-brochure.pdf) Discover Head-to-Head Data for Retevmo versus First-Line Standards of Care and Find Original Phase I/II Trial Results [See NSCLC Data](https://retevmo.lilly.com/hcp/efficacy/libretto-431) [See MTC Data](https://retevmo.lilly.com/hcp/efficacy/libretto-531) ![Retevmo: where precision and strength meet](https://retevmo.lilly.com/assets/img/retevmo-status-quo.png) # Retevmo: The first precision oncology treatment approved by the FDA for certain _RET_-driven solid tumors, regardless of type1,2 * * * ![NCCN recommends selpercatinib (Retevmo)](https://retevmo.lilly.com/assets/img/hcp-kcd-nccn-lung-thyroid-reco.svg) Selpercatinib (Retevmo) is a National Comprehensive Cancer Network® (NCCN®)-recommended treatment option for certain patients with _RET_-positive metastatic non-small cell lung cancer (NSCLC) and _RET_-positive advanced or metastatic thyroid carcinoma3,4\* [See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendations](https://retevmo.lilly.com/hcp/efficacy/libretto-001?section=nccn-guidelines) NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. \*The NCCN Guidelines provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories. See the NCCN Guidelines for detailed recommendations, including other preferred treatment options. The clinical data for Retevmo were from LIBRETTO-001, a phase I/II, multicohort, open-label, single-arm clinical trial.1,5 [Click here to explore clinical trial design](https://retevmo.lilly.com/hcp/efficacy/libretto-001). ## Retevmo is the first precision medicine approved specifically for patients with _RET_-driven advanced or metastatic solid tumors, regardless of tumor type1 ![Role of RET in RET-driven cancers such as RET fusions and RET point mutations](https://retevmo.lilly.com/assets/img/c-se-us-0281-se-hcp-pay-all-eff-summary-page_desktop.png) Up View Description _RET_ Fusions Locally Advanced or Metastatic NSCLC - treatment-naive patients (n=69): - 84% ORR (95% CI: 73, 92) - Median DoR: 20.2 months (95% CI: 13, NE) - previously treated patients (n=247): - 61% ORR (95% CI: 55, 67) - Median DoR: 28.6 months (95% CI: 20, NE) Advanced or Metastatic _RET_ Fusion-Positive Thyroid (Non-MTC) - systemic therapy-naive patients (n=24): - 96% ORR (95% CI: 79, 100) - Median DoR: not yet reached (95% CI: 42.8, NE) - previously treated patients (n=41) - 85% ORR (95% CI: 71, 94) - Median DoR: 26.7 months (95% CI: 12.1, NE) _RET_ Point Mutations Advanced or Metastatic MTC - cabozantinib/vandetanib-naive patients (n=88): - 81% ORR (95% CI: 71, 88) - Median DoR: not yet reached (95% CI: 51.3, NE) - previously treated patients (n=55): - 76% ORR (95% CI: 63, 87) - Median DoR: 45.3 months (95% CI: 29.9, NE) _RET_ Fusions Tumor Agnostic - patients with other advanced or metastatic solid tumors (n=41) - 44% ORR (95% CI: 28, 60) - Median DoR: 24.5 months (95% CI: 9.2, NE) - Evaluated in the largest phase I/II trial of patients with _RET_-driven cancers (N=796), including those with brain metastases1 - In patients with locally advanced or metastatic _RET_ fusion-positive NSCLC and measurable brain metastases (n=21), responses in intracranial lesions were observed in 86% of evaluable patients (4 of 5 treatment-naive patients and 14 of 16 previously treated patients). 39% and 38% of responders in the previously treated and treatment-naive cohorts, respectively, had a DoR of ≥12 months1†‡ - 8% of patients permanently discontinued treatment due to ARs. 3% were considered treatment-related, as assessed by trial investigator. ARs resulting in permanent discontinuation in ≥0.5% of patients included increased ALT (0.6%), fatigue (0.6%), sepsis (0.5%), and increased AST (0.5%)1,6 †Patients were treatment naive or previously treated with platinum-based chemotherapy and had measurable CNS lesions at baseline according to IRC assessment.1 ‡3 patients received RT to the brain within 2 months prior to study entry; 1 patient in the previously treated cohort and 2 patients in the treatment-naïve cohort.1 **Take action on _RET_. First, test. Then treat.** **Select Important Safety Information** The labeling for Retevmo contains Warnings and Precautions for **hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome (TLS), risk of impaired wound healing, hypothyroidism, embryo-fetal toxicity, and slipped capital femoral epiphysis/slipped upper femoral epiphysis (SCFE/SUFE) in pediatric patients**. Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to initiating Retevmo, every 2 weeks during the first 3 months of treatment, then monthly thereafter and as clinically indicated. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly, and as clinically indicated. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). See full Prescribing Information for further management instructions and dosage modifications for adverse reactions. Closely monitor patients that may be at risk of TLS (rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration) and consider appropriate prophylaxis including hydration. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. Monitor thyroid function before and periodically during treatment with Retevmo. Withhold until clinically stable or permanently discontinue Retevmo based on severity of hypothyroidism. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Advise females and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for at least 1 week after the last dose. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **IN LIBRETTO-001: Serious adverse reactions** occurred in 44% of patients who received Retevmo. The most frequent serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions** occurred in 3% of patients; fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Most common adverse reactions** (≥25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. **Most common Grade 3 or 4 laboratory abnormalities** (≥5%) were decreased lymphocytes, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium. ## LIBRETTO-001 Trial Design The phase I/II, multicohort, open-label, single-arm, multicenter LIBRETTO-001 trial evaluated Retevmo in patients with _RET_-altered advanced solid tumors. The pooled safety population included the following patients (n=796): advanced or metastatic _RET_ fusion-positive NSCLC§, advanced or metastatic _RET_ fusion-positive thyroid cancer (non-MTC), advanced or metastatic _RET_-mutant MTC, the tumor agnostic cohort of other locally advanced or metastatic _RET_-fusion positive tumors, including pancreatic and CRC‖. Additionally, the overall safety analysis included patients with other cancers, including cancers without a _RET_ alteration. The study evaluated the following cohorts for efficacy: systemic therapy-naive patients (n=69) and previously treated patients who had progressed on platinum-based chemotherapy (n=247¶) with advanced or metastatic _RET_ fusion-positive NSCLC; systemic therapy-naive (n=24\*\*††‡‡) and previously treated (n=41\*\*††§§) patients with advanced or metastatic _RET_ fusion-positive thyroid cancer (non-MTC); patients with advanced or metastatic _RET_-mutant MTC that were cabozantinib and vandetanib-naive (n=88††) and patients previously treated with cabozantinib and vandetanib (n=55††‖‖), and patients in the tumor agnostic cohort (n=41¶¶). Major efficacy outcomes were ORR and DoR. Other efficacy outcomes included CNS ORR, CNS DoR, PFS, OS, time to response, and best change in tumor size from baseline. In phase II, the dose for Retevmo was 160 mg PO BID.1-3 §Patients with advanced or metastatic _RET_ fusion-positive NSCLC who had progressed on platinum-based chemotherapy and those without prior systemic therapy were enrolled in separate cohorts.1 ‖Efficacy was evaluated in 41 patients, including those with the following tumor types: pancreatic adenocarcinoma (n=11); colorectal (n=10); salivary (n=4); unknown primary (n=3); breast (n=2); sarcoma (soft tissue) (n=2); xanthogranuloma (n=2); carcinoid (bronchial) (n=1); carcinoma of the skin (n=1); cholangiocarcinoma (n=1); ovarian (n=1); pulmonary carcinosarcoma (n=1); rectal neuroendocrine (n=1); small intestine (n=1).1 ¶Efficacy was evaluated in 247 adult patients with advanced or metastatic _RET_ fusion-positive NSCLC who were previously treated with platinum chemotherapy enrolled into a cohort of LIBRETTO-001. All 247 patients received systemic therapy (with a median of 2 prior systemic regimens). 144 of the 247 patients received prior anti-PD-1/PD-L1 therapy, and 85 of the 247 patients received a prior MKI.7 \*\*Non-MTC by histology included papillary (n=54), poorly differentiated (n=6), anaplastic (n=4), and Hurthle cell (n=1).1 ††Number of patients included in the initial efficacy analysis. Efficacy was based on patients who had at least 6 months of follow-up.7 ‡‡Patients in this cohort received no prior systemic therapy other than RAI.1 §§Patients in this cohort received a prior systemic therapy other than RAI.1 ‖‖The efficacy of Retevmo was evaluated in 55 patients with _RET_-mutant advanced MTC who were previously treated with cabozantinib or vandetanib enrolled into a cohort of LIBRETTO-001.1 ¶¶Patients in this cohort received prior systemic therapies with a median of 2 prior systemic therapies (range 0-9).1 BID=twice daily; CI=confidence interval; CR=complete response; DoR=duration of response; NE=not estimable; NSCLC=non-small cell lung cancer; ORR=objective response rate; PO=orally; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors; RET=rearranged during transfection. [See full trial results](https://retevmo.lilly.com/hcp/efficacy/libretto-001) **References: 1**. Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. **2.** Drilon A, Hu ZI, Lai GGY, et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. _Nat Rev Clin Oncol_. 2018;15(3):151-167. **3.** Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V11.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed October 15, 2024. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. **4.** Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 23, 2024. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. **5.** Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). https://clinicaltrials.gov/ct2/show/NCT03157128. Updated June 9, 2022. Accessed June 14, 2022. **6.** Data on File. Lilly USA, LLC. DOF-SE-US-0060. **7.** Drilon A, Subbiah V, Gautschi O, et al. Durability of efficacy and safety with selpercatinib in patients with RET fusion+ non-small-cell lung cancer: LIBRETTO-001. Poster presented at: European Lung Cancer Congress; March 30–April 2, 2022. Poster 27P. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Targeted Cancer Therapy [Skip to main content](https://retevmo.lilly.com/how-it-works#maincontent) # What is Retevmo? Retevmo is a targeted cancer therapy; it is not chemotherapy Targeted therapies aim to block the specific driver of your cancer. Retevmo is a prescription oral therapy that was designed to block the primary driver of tumor growth in _RET_-positive advanced non-small cell lung cancer (NSCLC), thyroid cancers, and certain other cancers. Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. RET=rearranged during transfection. ![How retevmo works](https://retevmo.lilly.com/assets/img/header_how_retevmo_works.jpg) ![Dripping faucet](https://retevmo.lilly.com/assets/img/dtc-faucet.png) ## How Retevmo works Retevmo is designed to turn off the production of RET in certain _RET_-driven cancers There are different genomic alterations, or changes, that may be driving your cancer. A genomic alteration means that the genes in some of your cells have changed and may be abnormal. An alteration may occur in a gene called _RET_ (rearranged during transfection). We all have RET in our bodies, similar to how we all have faucets in our homes. When a person has a _RET_ alteration, it’s like that faucet gets stuck in the “on” position, allowing water to spread, just as _RET_ alterations allow cancer to grow. Retevmo acts like a wrench that helps turn the faucet off. ## Learn more about how Retevmo works in certain _RET_-positive cancers Up View Description 00:00-00:14 \[Retevmo logo element rotates clockwise and indications appear on screen\] **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **INDICATIONS** What is Retevmo? Retevmo is a prescription medicine that is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy) - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options\* Your healthcare provider will perform a test to make sure that Retevmo is right for you. It is not known if RETEVMO is safe and effective when used: - in children younger than 2 years of age, or in children with other conditions. \*Retevmo was approved based on the percentage of patients whose tumor size shrank or disappeared after treatment and how long the response lasted. Studies are ongoing to confirm the benefit of Retevmo for this use. **_Please read and listen to the Indications and Safety Summary following this video._** _RET_ =rearranged during transfection. 00:14-00:34 \[Retevmo logo increases in size and slides to the center of the screen. Other text appears below it\] **Narrator:** Receiving your diagnosis and learning about your treatment options can be overwhelming. To help you better understand RETEVMO as a treatment option, this video will explain the importance of biomarker testing, what _RET_ is, and how RETEVMO works. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine In this video, you’ll learn about - Biomarker testing - _RET_ gene - How Retevmo works _RET_ =rearranged during transfection. 00:34-01:17 \[T-shaped pieces of DNA strands float into frame against a blue background. These pieces join and wind together to form double spirals, the shape of DNA.\] **Narrator:** Not everyone's cancer is the same. Certain cancers can be driven by a genomic alteration or change in your cancer's DNA. A genomic alteration means the genes in some cells have changed and may be cancerous. If your cancer is driven by a genomic alteration, there may be additional treatment options available to you. To see if your cancer is being driven by an alteration, your doctor will need to order a biomarker test. Certain biomarker tests require your doctor to biopsy the tumor, which means removing some tissue or blood for testing. If your tumor has been biopsied previously, some tissue may already be available for testing. 01:17-01:37 \[A round cell (healthy cell) floats and revolves in the center of the frame. It has rod-shaped structures on its surface. The _RET_ gene is shown as red dots produced by the rods. Lights on these rods begin to flash and blink as they produce more _RET_. This process continues as the cell divides into two\] **Narrator:** After your biomarker test is completed, you will start to learn if your cancer is driven by a genomic alteration. An alteration may occur in a gene called _RET_. But what exactly is _RET_? **_RET_** or "rearranged during transfection" is a gene that everyone has and produces in their body. **Caption:** Healthy cell. _RET_ (pointing to a red _RET_ image inside the cell). 01:37-01:56 \[All the rods on both cells now start producing _RET_. The lights on some of these rods stay on continuously instead of blinking. The red dots representing _RET_ collect in the cells, which are simultaneously and uncontrollably multiplying. Blood vessels wind their way through the mass of multiplying cells as they form a cancerous tumor\] **Narrator:** Normally, your body is able to manage the production of _RET_. But when your body has a _RET_ alteration it can't control or turn off how much _RET_ is produced. This can cause a _RET_-positive tumor to form. There are treatment options approved to treat _RET_-positive cancers. 01:56-02:09 \[Small purple globes of Retevmo float into the frame and are absorbed by the cancerous cells. The frame zooms into one of the cells. Once within the cell, the Retevmo bubbles fit into the ends of some of the rods, like a key into a lock. This turns off the light on the rod (which were previously either flashing or continuously on), and stops the production of _RET_\] **Narrator:** One of those treatments is Retevmo. Retevmo was designed to work by slowing or stopping the overproduction of _RET_ in these cancerous cells, which may stop or slow a tumor's growth. **Caption:** Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. Retevmo® \| selpercatinib 02:09-02:30 \[The cancer cell begins to wither and shrink in size, slowly fragmenting into pieces and then disappearing as Retevmo exerts its action. Other cells also meet the same fate\] **Narrator:** Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. Retevmo is a targeted therapy, which means it is designed to turn off the production of _RET_ in certain _RET_-driven cancers. Targeted therapies aim to block the specific driver of your cancer, such as _RET_. **Caption:** Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. 02:30-02:38 \[Many purple bubbles of Retevmo merge to form the 160 mg tablet. The 120 mg, 80 mg, and 40 mg tablets also appear one after the other, in a line on the screen\] **Narrator:** Retevmo is not a chemotherapy, immunotherapy, or radiation therapy, and can be taken at home. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 02:38-02:50 \[The tablets continue to stay on screen. Retevmo logo appears at the bottom left of the screen; Lilly logo appears at bottom right of the screen\] **Narrator:** Retevmo is taken orally by itself and not in combination with additional cancer therapies. Talk to your doctor and see if Retevmo may be a treatment option for you. **Caption:** For visual representation only; tablets shown are not actual size. TALK TO YOUR DOCTOR AND SEE IF RETEVMO MAY BE A TREATMENT OPTION FOR YOU 02:50-17:17 **Narrator and Caption:** **INDICATIONS AND SAFETY SUMMARY** RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. **Warnings - RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [www.fda.gov/medwatch](https://www.fda.gov/medwatch).** **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://www.retevmo.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** SE CON BS ALL 27SEP2024 **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 17:18-17:27 \[Red Lilly logo in middle left of screen; Retevmo logo in middle right of screen\] **Caption:** Lilly \| A MEDICINE COMPANY Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine Retevmo® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. PP-SE-US-1552 12/2024 ©Lilly USA, LLC 2024. All rights reserved. [Ask your doctor](https://retevmo.lilly.com/what-is-ret?section=talk-to-doctor) about biomarker testing for _RET_ and see if Retevmo is right for you **SELECT SAFETY INFORMATION** **RETEVMO may cause serious side effects, including:** **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your doctor right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever [Retevmo in NSCLC](https://retevmo.lilly.com/about-mnsclc) See how Retevmo may help people living with _RET_-positive advanced NSCLC [Retevmo in thyroid cancer](https://retevmo.lilly.com/about-mtc) See how Retevmo may help people living with _RET_-positive advanced thyroid cancer [Retevmo in other cancers](https://retevmo.lilly.com/other-cancers) See how Retevmo may help people living with certain other _RET_-positive advanced cancers Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo for Advanced Cancers [Skip to main content](https://retevmo.lilly.com/other-cancers#maincontent) ![Learn more about Retevmo in MTC](https://retevmo.lilly.com/_nuxt/img/transparency.6ce42a6.png) Scroll Down Down ![Learn more about Retevmo in MTC](https://retevmo.lilly.com/assets/img/dual_indication_campaign_dtc.jpg) # What does it mean if my advanced cancer is _RET_-positive? Certain advanced cancers can be driven by a gene in your body. One of those genes is _RET_. There are many different types of advanced cancers that can be driven by _RET_, including pancreatic cancer, colon cancer, and breast cancer. [Talk to your doctor](https://retevmo.lilly.com/what-is-ret?section=talk-to-doctor) to see if your cancer is _RET_-positive. RET=rearranged during transfection. Retevmo is available for certain _RET_-positive advanced cancers ## Retevmo may help by targeting what is driving your _RET_-positive advanced cancer Retevmo was studied in the largest clinical trial of people with _RET_-positive cancers. The trial included people with certain advanced cancers, like pancreatic cancer, colon cancer, and breast cancer, and all had tumors that were eligible to be evaluated for shrinkage. The trial evaluated how many people responded to treatment, which means their tumors either shrank or disappeared completely, and how long the response lasted. Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. ## **Retevmo has been shown to shrink tumors in some adults with certain _RET_-positive advanced cancers** ![44%](https://retevmo.lilly.com/assets/img/shrink-ratio.png) **of the 41 people had an objective response, meaning their tumors shrank by 30% or more** - **Responses lasted a median\* of 24.5 months** \*Median is the middle number in a range of numbers. **SELECT SAFETY INFORMATION** **RETEVMO may cause serious side effects, including:** **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your doctor if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure and the need for dialysis treatment, an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures Learn how to take Retevmo [Retevmo dosing](https://retevmo.lilly.com/taking-retevmo) Read more about what could be driving your cancer [What is _RET_?](https://retevmo.lilly.com/what-is-ret?section=what-is-ret) Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo Patient Story [Skip to main content](https://retevmo.lilly.com/patient-stories#maincontent) # Retevmo Patient Story Meet Ilana, a real Retevmo patient When Ilana was 52 years old, she was unexpectedly diagnosed with non-small cell lung cancer (NSCLC). When her cancer spread, a biomarker test revealed that she was _RET_-positive, making her eligible for Retevmo. ![Ilana, a real Retevmo patient](https://retevmo.lilly.com/assets/img/patient-stories-header.jpg) **Chapter 1** Meet Ilana, a mother of 5 who’s an active member of her community in Texas and loves spending time outdoors with her family. Up View Description 00:00-00:15 \[Retevmo logo element rotates clockwise\] **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** What is Retevmo? Retevmo is a prescription medicine that is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. Your healthcare provider will perform a test to make sure that Retevmo is right for you. It is not known if Retevmo is safe and effective when used in children. **Caption:** Individual results may vary. Ilana is an actual Retevmo patient with _RET_-positive metastatic non-small cell lung cancer (NSCLC). Talk to your doctor to see if Retevmo is right for you. Patient was compensated for her time. RET=rearranged during transfection. **Caption:** _Please read and listen to the Indication and Safety Summary following this video._ 00:15-00:16 **Caption:** Ilana’s Story 00:16-00:22 **Caption:** Chapter I MY HAPPY PLACE 00:22-00:26 \[Ilana sits outdoors, surrounded by mountains on the bank of a flowing stream, accompanied by her dog.\] Ilana: **I live life now through the lens of thinking, "If I were a memory…** 00:27-00:35 \[Ilana sits in her living room with windows and bookshelves behind her.\] **Ilana (continuing): …How do I want them to remember me? What I want them to get from me." And that makes life very different.** 00:37-00:41 \[A video production assistant claps a scene marker in front of Ilana’s smiling face.\] **Ilana: I'm Ilana, lucky mother of five precious kids.** 00:41-00:47 \[Montage of Ilana’s family vacation videos: kids racing on the beach, sledding down a hill, and recording themselves singing together in the woods.\] **Audio: Happy family chatter** 00:47-00:52 \[Ilana seated in her living room.\] **Ilana: My family is everything.** 00:52-01:10 \[Ilana and her family ride their bicycles through their neighborhood. Ilana in the kitchen helps her daughters with their homework and puts together their school lunches.\] **Ilana: The love and support and care and joy. I want to be here for weddings. I want to be here to help them with their babies. I want to be here for graduations. I want to be here to help with homework or answer questions or put exactly what they like in their school lunch.** 01:10-01:11 \[The camera focuses on a note which Ilana has left on top of one of the lunchboxes, inside the main pouch. The note says “Camila, You truly are a “rock star” today. Enjoy! I love you, Mama”.\] **Ilana: Put the right note for that day.** 01:11-01:16 \[Ilana in the kitchen oils a pan to make eggs and pancakes.\] **Ilana’s daughter: Hey, Mom, what's for breakfast?** **Ilana: Hey, baby. Eggs and pancakes and fruit.** 01:16-01:28 \[Ilana seated in her living room. Scenes of sunlight spangling through tree limbs, water flowing in stream, Ilana letting the stream water flow over her hand.\] **Ilana: If I could probably pick to do anything, I'd pick to go hiking and just be in the quiet of nature. Listening to the leaves rustle or the stream. It's just grounding.** 01:28-01:35 \[Ilana seated in her living room.\] **Ilana: Especially with all this going on, it just feels good to just be, and be in nature.** 01:36-01:53 \[Ilana in a park with her family, playing with their dog.\] **Ilana: The community is what feeds my soul. It's people loving my children like their own, so they barely notice I'm gone. It's my husband showing up in a little bit after working all night long in the hospital and being 100% in it.** 01:54-02:01 \[Ilana seated in her living room.\] **Ilana: I get a lot of joy out of just watching the joy and love around me. That's my happy place.** 02:01-02:16 \[Ilana and her family riding their bicycles in the neighborhood.\] **Ilana: Because you don't know what tomorrow brings, really. Like a cancer diagnosis helps you to see that, make that very real. And it's really all that matters. It's all this. There's nothing else.** 02:16-02:19 \[The screen flickers as if a “home movie” is ending.\] 02:19-02:45 \[Retevmo logo in bottom-left of screen; red Lilly logo in bottom right of screen\] **Narrator: INDICATION AND SAFETY SUMMARY** RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. Your healthcare provider will perform a test to make sure that RETEVMO is right for you. It is not known if RETEVMO is safe and effective when used in children. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 02:45-07:44 **Narrator: Warnings - RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your doctor should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 07:44-09:23 **Narrator: Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for 1 week after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 09:23-09:45 **Narrator: These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [www.fda.gov/medwatch](https://www.fda.gov/medwatch).** **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 09:45-11:43 **Narrator: Before using** Before taking RETEVMO, tell your doctor about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 11:43-13:14 **Narrator: How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:14-13:38 **Narrator: Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to **www.Retevmo.com.** **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:38-14:08 **Narrator:** This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. **Caption:** SE CON BS LC 27SEP2024 **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 14:08-14:16 **Narrator:** RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 14:16-14:19 \[Red Lilly logo in middle left of screen; Retevmo logo in middle right of screen\] **Caption:** Lilly \| A MEDICINE COMPANY **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Retevmo® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** PP-SE-US-1522 11/2024 ©Lilly USA, LLC 2024. All rights reserved. **Chapter 2** Ilana's life was turned upside down when she was diagnosed with NSCLC. After a year, she learned that the cancer had spread and it was time to explore new options. Up View Description 00:00-00:15 \[Retevmo logo rotates clockwise\] **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** What is Retevmo? Retevmo is a prescription medicine that is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread Your healthcare provider will perform a test to make sure that Retevmo is right for you. It is not known if Retevmo is safe and effective when used in children. **Caption:** Individual results may vary. Ilana is an actual Retevmo patient with _RET_-positive metastatic non-small cell lung cancer (NSCLC). Talk to your doctor to see if Retevmo is right for you. Patient was compensated for her time. RET=rearranged during transfection. **Caption:** _Please read and listen to the Indication and Safety Summary following this video._ 00:15-00:17 **Caption:** Ilana’s Story 00:17-00:20 **Caption:** Chapter II – A SAD TRUTH 00:20-00:21 \[A young girl in a kitchen talks about the friendship bracelets on her arm.\] **Girl: This one was from…** 00:21-00:25 \[The camera pans to reveal the face of Ilana.\] **Girl: …someone at camp, and this one was from my counselor at camp.** 00:25-00:26 \[Another young girl smiles and waves at camera\] **Girl: This one was from a friend.** 00:26-00:29 \[The young girl is seen to be having a conversation with Ilana at the dining table.\] **Ilana: I started coughing when I was pregnant with the twins,** 00:29-00:32 \[Various photos of twin girls; video of girls with their mother; overlaid on children’s drawings in background.\] **Ilana: and I had it looked at during that pregnancy.** 00:32-00:44 \[Ilana hugs girls outside a school and exchanging pecks on the cheeks.\] **Ilana: I mean, I had it looked at on and off for over eight years. It turns out the cough had nothing to do with the cancer, but thank goodness I coughed because it's what let me know that you know, it's what made me look into it.** 00:44-01:03 \[Ilana on couch in living room; camera cuts quickly to close-up of Ilana’s eyes, hands as she stands outdoors amidst trees.\] **Ilana: I was diagnosed with metastatic non-small cell lung cancer and the feeling was... scared... alone... It's terrifying. It's shocking because you are alone.** 01:03-01:11 \[Ilana sitting in living room on the couch.\] **Ilana: Like everybody's around you and everybody loves you. But life for everybody goes on if you die. And while that's my…** 01:11-01:18 \[Camera cut to backyard swimming pool. Daughter sitting on beach surrounded by baby sea turtles; cut to home movie of girls playing projected onto Ilana in a darkened room.\] **Ilana: …deepest wish, my biggest fear was dying. And not being here to be with the people I love.** 01:21-01:25 \[Close up of vegetable garden; metal placard reads “Camila’s Garden” and withering plants.\] **Ilana: I was told at one point that my chance of survival was very low.** 01:26-01:39 \[Ilana sitting in living room; cut to close up of dripping faucet; cut to kitchen with dirty dishes with the swimming pool in the background.\] **Ilana: And it... it made me sick. Like I got sick and I almost passed out in front of my three little kids and one morning while I was making them breakfast.** 01:40-01:42 \[Darkened house with dog whimpering; cut to Ilana with her husband; cut to girls playing in soccer game at night.\] **Ilana: There was a time when I couldn't go hiking and I just couldn't do what I wanted to do. And I wondered if, you know, would I make it to the next soccer game…** 01:51-01:59 \[Girls dancing; Ilana hugging her adult son.\] **Ilana: …or dance recital or even to my son's wedding. Like, how could I possibly not be at the wedding?** 02:00-02:02 \[Video of treetops, with screen within screen showing more treetops.\] **Ilana: My lung surgery was quick and sweet,** 02:02-02:22 \[Ilana seen from the side view sitting in living room with a mirror on the wall in the background; cut to Ilana with front view with a bookshelf in the background\] **Ilana: …and then we learned that it was in two lymph nodes. So l had to do chemo and they found it in my liver. I had liver surgery. I thought that was all. I then found out it had gone to my brain. I mean, I don't even know what the words are to explain. When you hear, "brain tumor." Like, it doesn't get worse than that.** 02:22-02:26 \[Ilana sits on couch with her two girls sharing a blanket; cut to preparing meals around the house; cut to Ilana sitting on a swing with her kids; cut to kids playing in the backyard on a see-saw; cut to hosting a birthday party.\] **Ilana: And I still had to wake up every morning and be okay for my kids and lay in bed every night and cry with my husband.** 02:29-02:34 \[Husband reads a story to daughter; sound of film reel coming to an end and screen fades to white.\] **Audio: Dan reads a story to his daughter** 02:34-08:01 \[Retevmo logo in bottom-left of screen; red Lilly logo in bottom right of screen\] **Narrator: INDICATION AND SAFETY SUMMARY** RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. Your healthcare provider will perform a test to make sure that RETEVMO is right for you. It is not known if RETEVMO is safe and effective when used in children. **Warnings - RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your doctor should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 08:01-11:59 **Narrator: Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [www.fda.gov/medwatch](https://www.fda.gov/medwatch).** **Before using** Before taking RETEVMO, tell your doctor about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - **During treatment with RETEVMO, you should avoid taking:** - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 11:59-14:24 **Narrator: How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to **www.Retevmo.com**. This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. **Caption:** SE CON BS LC 27SEP2024 **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 14:24-14:32 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 14:32-14:36 \[The screen fades to red Lilly logo in middle left of screen; Retevmo logo in middle right of screen\] **Caption:** Lilly \| A MEDICINE COMPANY **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Retevmo® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** PP-SE-US-1523 11/2024 ©Lilly USA, LLC 2024. All rights reserved. **Chapter 3** Through biomarker testing, Ilana discovered that she was _RET_-positive. Though _RET_ is a less common mutation, this diagnosis meant she was eligible to take Retevmo. Up View Description 00:00-00:15 \[Retevmo logo element rotates clockwise\] **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** What is Retevmo? Retevmo is a prescription medicine that is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread Your healthcare provider will perform a test to make sure that Retevmo is right for you. It is not known if Retevmo is safe and effective when used in children. **Caption:** Individual results may vary. Ilana is an actual Retevmo patient with _RET_-positive metastatic non-small cell lung cancer (NSCLC). Talk to your doctor to see if Retevmo is right for you. Patient was compensated for her time. RET=rearranged during transfection. **Caption: _Please read and listen to the Indication and Safety Summary following this video_.** 00:15-00:17 **Caption:** Ilana’s Story 00:17-00:22 **Caption:** Chapter III – THE TRUE TEST 00:22-00:26 \[City skyline in twilight in the background\] **Ilana: I walked into the kids' room and they were little and sleeping.** 00:27-00:33 \[Ilana sitting on couch in living room\] **Ilana: And I just looked at them and thought, "How long will I be here?"** 00:34-00:44 \[Ilana’s daughters playing on a trampoline in their backyard\] **Ilana: Will I get to see them grow up? Will I be here, you know, in four months? Will I be here in six months? You know, like…** 00:44-00:46 \[Ilana’s daughters jumping in a muddy puddle in a park\] **Ilana: …how long do I have to tell them…** 00:46-00:49 \[Ilana sitting on couch in living room\] **Ilana: …what I want to give them during that time?** 00:50-00:56 \[Ilana cuddling with her daughter\] **Ilana: You know, nobody else knows how to hold one of them when they're feeling really sad.** 00:56-00:59 \[Ilana sitting on couch in living room\] **Ilana: You know, nobody else is the mom. So...** 00:59-01:05 \[Ilana with girls working in the garden\] **Ilana: When I was diagnosed…** 01:05-01:21 \[Ilana putting on hiking boots and then going hiking by a river in winter, alone\] **Ilana: …it was a shock because I was healthy. That's the weird thing about cancer. You're healthy until you're really not. You know, initially, Dan used to tell me it's going to be okay. And that made me crazy because he had no way to know.** 01:21-01:28 \[Ilana sitting by the river after her hike, soaking up the winter sun\] **Ilana: Nobody can tell you it's going to be okay. Thankfully, a friend of mine told me about biomarker testing.** 01:28-01:32 \[Close-up of a bunch of violet flowers on their stalk\] **Ilana: So I talked to my doctor about it and I was able to get tested.** 01:32-01:45 \[Ilana’s daughters gardening\] **Ilana: Thanks to the test, I found out that my tumor was RET-positive. It meant that I had a biomarker that could be treated with RETEVMO.** 01:45-01:48 \[Ilana sitting on couch in living room\] **Ilana: You know and I just feel like it's going to be okay.** 01:48-02:05 \[Ilana working in the garden with daughters, who spray her with a hose; sound of film reel coming to an end and screen fades to white\] **Ilana: And every step of the journey, and it's been treatable, which is amazing.** 02:05-02:30 \[Retevmo logo in bottom-left of screen; red Lilly logo in bottom right of screen\] **Narrator: INDICATION AND SAFETY SUMMARY** RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. Your healthcare provider will perform a test to make sure that RETEVMO is right for you. It is not known if RETEVMO is safe and effective when used in children. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 02:30-07:30 **Narrator: Warnings - RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your doctor should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 07:30-09:10 **Narrator: Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 09:10-09:32 **Narrator: These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.** **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 09:32-11:29 **Narrator: Before using** Before taking RETEVMO, tell your doctor about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 11:29-13:01 **Narrator: How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:01-13:26 **Narrator: Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to **www.Retevmo.com.** **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:26-13:55 **Narrator:** This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. **Caption:** SE CON BS LC 27SEP2024 **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:55-14:03 **Narrator:** RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 14:03-14:08 \[Red Lilly logo in middle left of screen; Retevmo logo in middle right of screen\] **Caption:** Lilly \| A MEDICINE COMPANY **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Retevmo® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** PP-SE-US-1524 11/2024 ©Lilly USA, LLC 2024. All rights reserved. **Chapter 4** From diagnosis to today, Ilana discusses how NSCLC and a _RET_-positive diagnosis have changed her perspective on what’s most important in life. Up View Description 00:00-00:15 \[Retevmo logo element rotates clockwise\] **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** What is Retevmo? Retevmo is a prescription medicine that is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. Your healthcare provider will perform a test to make sure that Retevmo is right for you. It is not known if Retevmo is safe and effective when used in children. **Caption:** Individual results may vary. Ilana is an actual Retevmo patient with _RET_-positive metastatic non-small cell lung cancer (NSCLC). Talk to your doctor to see if Retevmo is right for you. Patient was compensated for her time. RET=rearranged during transfection. **Caption: _Please read and listen to the Indication and Safety Summary following this video_.** 00:15-00:18 **Caption:** Ilana’s Story 00:18-00:21 **Caption:** Chapter IV – A GIFT 00:21-00:36 \[Ilana hiking in winter attire amidst trees; swinging from a tree branch, then from a trapeze line; Ilana with daughters\] **Ilana: I'm so grateful that I found out that I was _RET_ positive, and that I have access to treatments that allow me to live really happy and allowing me to enjoy my family and my community and my friends and my world.** 00:36-00:38 \[Ilana playing with her daughter outdoors\] **Ilana: It's a gift.** 00:38-00:47 \[Ilana and husband mingling with guests at a party\] **Ilana: I want people to really know that the targeted medicines like RETEVMO exist and that biomarker testing is essential.** **Caption:** Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious. 00:47-00:52 \[Ilana sitting on couch in living room\] **Ilana: And it's not that the fear ever goes away. Because it's real and it's scary.** 00:52-00:58 \[Ilana partying with her family in their backyard by the pool at night clicking polaroid shots\] **Ilana: That's what keeps me apologizing to my kids when I use a voice I didn't want to use.** 00:58-01:09 \[Ilana and her husband hugging and kissing as their daughter takes their photo\] **Ilana: That's what keeps me making a point to make dates with my husband, because there is the reality of having a disease that is unpredictable.** 01:09-01:12 \[Ilana and her husband mingling with guests at a party\] **But you know what, I wake up every day…** 01:13-01:28 \[Ilana and her family having a pillow fight, laughing together\] **Ilana: …You know, joyful and ready to be with my children and my husband and my wonderful village of precious friends who, you know, just support us. And we're just a community and…** 01:28-01:40 \[Ilana sitting on couch in living room\] **Ilana: life's fragile. And we're lucky to be alive and together and healthy and planning weddings and, you know, crying over scraped knees and, you know, just living life.** 01:40-01:52 \[Ilana standing with her family, smiling and laughing in a party\] 01:52-02:17 \[Retevmo logo in bottom-left of screen; red Lilly logo in bottom right of screen\] **Caption: INDICATION AND SAFETY SUMMARY** RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. Your healthcare provider will perform a test to make sure that RETEVMO is right for you. It is not known if RETEVMO is safe and effective when used in children. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 02:17-07:18 **Narrator: Warnings - RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your doctor should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 07:18-08:57 **Narrator: Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 08:57-09:19 **Narrator: These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.** **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 09:19-11:16 **Narrator: Before using** Before taking RETEVMO, tell your doctor about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 11:16-12:48 **Narrator: How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 12:48-13:13 **Narrator: Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to **www.Retevmo.com.** **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:13-13:42 **Narrator:** This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. **Caption:** SE CON BS LC 27SEP2024 **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:42-13:50 **Narrator:** RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Lilly \| A MEDICINE COMPANY 13:50-13:56 \[Red Lilly logo in middle left of screen; Retevmo logo in middle right of screen\] **Caption:** Lilly \| A MEDICINE COMPANY **Caption:** Retevmo® \| selpercatinib tablets \| 40 mg • 80 mg • 120 mg • 160 mg \| A Lilly Medicine **Caption:** Retevmo® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. **Caption:** PP-SE-US-1525 11/2024 ©Lilly USA, LLC 2024. All rights reserved. [Ask your doctor](https://retevmo.lilly.com/what-is-ret?section=talk-to-doctor) about biomarker testing for _RET_ and see if Retevmo is right for you **SELECT SAFETY INFORMATION** **RETEVMO may cause serious side effects, including:** **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your doctor if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your doctor should tell you when you may start taking RETEVMO again after surgery. [Retevmo in NSCLC](https://retevmo.lilly.com/about-mnsclc) See how Retevmo may help people living with _RET_-positive advanced NSCLC [Retevmo in thyroid cancer](https://retevmo.lilly.com/about-mtc) See how Retevmo may help people living with _RET_-positive advanced thyroid cancer [Retevmo in other cancers](https://retevmo.lilly.com/other-cancers) See how Retevmo may help people living with certain other _RET_-positive advanced cancers Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo Savings Support [Skip to main content](https://retevmo.lilly.com/savings-support#maincontent) Information To continue using a Savings Card in 2025, eligible patients can download now under the [Savings & Support Page](https://retevmo.lilly.com/savings-support). # Savings & Support Resources See how you may be able to save on Retevmo and get support along the way ![Retevmo patients](https://retevmo.lilly.com/assets/img/dtc-header_savings_and_support_resources.jpg) ![Retevmo savings card](https://retevmo.lilly.com/assets/img/savings-support-savings-icon.png) ## Retevmo Savings Card **Eligible commercially insured covered patients pay as little as $0 a month\*** \*Month is defined as 30 days. **Governmental beneficiaries excluded, terms and conditions apply.** Paying for treatment shouldn’t be an additional concern for you and your loved ones, so we’ve created the Retevmo Savings Card, which may help you manage treatment costs. Need a Savings Card? [Download Savings Card](https://retevmo.lilly.com/savings-support#) By enrolling in and using the Retevmo Savings Card Program (“Program”) and using the Retevmo Savings Card (“Card”), you attest that you meet the eligibility criteria, and you agree to comply with the terms and conditions described below: **Card Eligibility:** 1. You have been prescribed Retevmo® (selpercatinib) for an approved use consistent with FDA-approved product labeling; 2. You are enrolled in a commercial drug insurance plan and have coverage for Retevmo: 3. **You are not enrolled in any state, federal, or government funded healthcare program, including, without limitation, Medicaid, Medicare, Medicare Part D, Medicare Advantage, Medigap, DoD, VA, TRICARE®/CHAMPUS, or any state prescription drug assistance program;** 4. You are a resident of the United States or Puerto Rico; and 5. You are 18 years of age or older. **Card Terms and Conditions** For patients with commercial drug insurance coverage for Retevmo: You must have commercial drug insurance that covers Retevmo and a prescription for an approved use consistent with FDA-approved product labeling to pay as little as $0 for a 1-month prescription fill of Retevmo. Month is defined as 30-days. Card savings are subject to a maximum monthly savings of wholesale acquisition cost plus usual and customary pharmacy charges and separate maximum annual savings of up to $9,200 per calendar year. Card may be used for a maximum of up to 14 prescription fills per calendar year. Except where prohibited by applicable state law, Card monthly and annual savings are reduced if Lilly identifies that you are enrolled in a plan or program, sometimes called a maximizer plan, that adjusts your cost sharing amount to be equal to or include some portion of the savings provided by the Card and attempts to prevent the savings from this Card from being applied to your out-of-pocket costs, including but not limited to copayments, coinsurances, and deductibles (“Maximizer”). If the Program identifies you are enrolled in a Maximizer, Card savings are reduced to a maximum monthly savings of up to $25 and a separate maximum annual savings of up to $350 per calendar year. If you have reason to believe that the Program erroneously identified enrollment in a Maximizer, please call the Retevmo Savings Card Program at 1-866-615-3716. Subject to Lilly USA, LLC’s (“Lilly”) right to terminate, rescind, revoke, or amend Card eligibility criteria and/or Card terms and conditions which may occur at Lilly’s sole discretion, without notice, and for any reason. Card expires and savings end on 12/31/2025. **Additional Program Terms and Conditions** If you have an insurance plan that is participating in an alternate funding program (“AFP”) that requires you to apply to the Retevmo Savings Card Program or otherwise pursue specialty drug prescription coverage through an alternate funding vendor as a condition of, requirement for, or prerequisite to coverage of Retevmo, you are not eligible for and are prohibited from using the Retevmo Savings Card Program. AFPs include programs where coverage, reimbursement, or patient out of pocket costs for a product in some way vary based on the availability of a manufacturer co-pay program. AFPs may modify, delay, deny, restrict, or withhold insurance benefits or coverage from patients, or exclude Lilly products from coverage contingent upon a member’s use of Retevmo Savings Card Program. You agree to inform the Retevmo Savings Card Program if you are or become a member of such an alternative funding program. You are responsible for any applicable taxes, fees, and any amount that exceeds the monthly or annual maximum Card savings. Monthly and annual maximum savings are set at Lilly’s sole and absolute discretion and may be changed with or without notice at any time for any reason. At its sole discretion and with or without notice, Lilly may reduce, eliminate, or otherwise modify the Card savings for any reason, including but not limited to if your commercial drug insurance plan imposes additional requirements which limits or prevents you from receiving coverage for Retevmo, only allows partial coverage for Retevmo, removes coverage for Retevmo and requires you to utilize the Card, does not provide a material level of financial assistance for the cost of Retevmo, or does not apply Card payments to satisfy your co-payment, deductible, or coinsurance for Retevmo. Card savings are not valid for: Massachusetts residents if an AB-rated generic equivalent is available; California residents if an FDA-approved therapeutic equivalent is available. You must meet the Card eligibility criteria, terms and conditions every time you use the Card. If at any time you begin receiving drug coverage under any state, federal, or government funded healthcare program, you understand that you will no longer be eligible for the Retevmo Savings Card and agree to call the Retevmo Savings Card Program at 1-866-615-3716 to stop participation. Card activation is required. You may not seek reimbursement from your health insurance, any third party, or any health savings, flexible spending, or other healthcare reimbursement accounts, for any amount of the savings received through the Card. By utilizing the Card, you agree that if you are required to do so under the terms of your insurance coverage for this prescription or are otherwise required to do so by law, you will notify your Insurance Carrier of your redemption of the Card. Card savings cannot be combined or utilized with any other program, discount, discount card, cash discount card, coupon, incentive, or similar offer involving Retevmo. You agree that this Card savings is intended solely for the benefit of you, the patient, and that the Card benefits are nontransferable. It is prohibited for any person to sell, purchase, or trade; or to offer to sell, purchase, or trade, or to counterfeit the Card. **THIS CARD IS NOT INSURANCE**. Lilly has the sole right to interpret and apply Card eligibility criteria, and terms and conditions. Card eligibility, and terms and conditions may be terminated, rescinded, revoked, or amended by Lilly at any time without notice and for any reason. Lilly’s sole discretion to terminate, rescind, revoke, or amend Card eligibility and/or Card terms and conditions includes the right to terminate any individual Card if Lilly determines, in its sole discretion, that a patient does not satisfy the Card’s eligibility criteria or is using or has attempted to use the Card inconsistently with these terms and conditions. Eligibility criteria, and terms and conditions for the Retevmo Savings Card Program may change from time to time; the most current version can be found at [https://retevmo.lilly.com/savings-support](https://retevmo.lilly.com/savings-support). You may be required to obtain a new Card, including if any Card terms and conditions have been terminated, rescinded, revoked, or amended by Lilly. Card void where prohibited by law. Subject to Lilly’s right to terminate, rescind, revoke or amend Card eligibility criteria and/or Card terms and conditions which may occur at Lilly’s sole discretion, without notice, and for any reason. Card expires and savings end on 12/31/2025. TRICARE® is a registered trademark of the Department of Defense (DoD), DHA. ## Filling your prescription There are multiple ways to get Retevmo, depending on your insurance. You may receive your medication from your hospital, your doctor, or from a specialty pharmacy. ![Specialty pharmacy icon](https://retevmo.lilly.com/assets/img/savings-support-specialty-pharmacy-icon.png) **Here’s how a specialty pharmacy works with you to fill your Retevmo prescription:** - Your doctor sends your prescription to a specialty pharmacy - The specialty pharmacy will call you to schedule a date and time to deliver your Retevmo medication (you may not recognize the phone number) - The specialty pharmacy can also help assess your eligibility for the [Retevmo Savings Card](https://retevmo.lilly.com/savings-support?section=savings-card)† †This offer is invalid for patients without commercial drug insurance or those whose prescription claims are eligible to be reimbursed, in whole or in part, by any governmental program. [Terms and conditions apply for eligible patients](https://retevmo.lilly.com/savings-support#). Lilly Support Services™ for Retevmo can help you find the specialty pharmacy with the lowest out-of-pocket cost ## Learn more about Retevmo ![Brochures on how Retevmo works](https://retevmo.lilly.com/assets/img/savings-support-patient-brochures.jpg) See how Retevmo works, how to take it, and some side effects you may experience with treatment. Download the brochure below. [Download the Patient Brochure\\ \\ Download](https://retevmo.lilly.com/assets/pdf/all-indications-patient-brochure.pdf) ![Share your Retevmo experience for yourself or a loved one](https://retevmo.lilly.com/assets/img/savings-support-share-experience.png) ## Share your Retevmo experience If you or a loved one has been treated with Retevmo and you would like to share your story, please call Lilly Support Services™ at [1-800-LillyRx (1-800-545-5979)](tel:1-800-545-5979). [Hear a real story from a real patient taking Retevmo](https://retevmo.lilly.com/patient-stories) ## Support groups Connect with others in your community who understand your diagnosis You are not alone on this cancer journey. There are organizations that can connect you with opportunities and support.‡ ![American Lung Association and Lung Force logos](https://retevmo.lilly.com/assets/img/ala-logo.jpg) [American Lung Association](https://www.lung.org/) ® is the leading organization working to save lives by improving lung health and preventing lung disease through education, advocacy, and research. The Lung Association is committed to defeating lung cancer and supporting those affected by it. ![Go2 Foundation for Lung Cancer logo](https://retevmo.lilly.com/assets/img/logo-go2-foundation.png) [GO2 Foundation for Lung Cancer](https://www.go2foundation.org/) ® transforms survivorship as the world’s leading organization dedicated to saving, extending, and improving the lives of those vulnerable, at risk, and diagnosed with lung cancer. ![The Happy Lungs Project](https://retevmo.lilly.com/assets/img/happy_lungs_logo.png) [The Happy Lungs Project](https://happylungsproject.org/) is patient driven 501c3 public charity committed to supporting researchers and clinicians in their work toward finding a cure for RET Positive Non-Small Cell Lung Cancer, while providing helpful information to empower patients in their own healing and journey. ![Lungevity logo](https://retevmo.lilly.com/assets/img/logo-lungevity.png) [LUNGevity Foundation](https://lungevity.org/) ®, the nation's leading lung cancer-focused nonprofit, is committed to making an immediate impact on increasing quality of life and survivorship of people with lung cancer by accelerating research into early detection and more effective treatments, as well as by providing community, support, and education for all those affected by the disease. ![RetPositive logo](https://retevmo.lilly.com/assets/img/logo-ret-positive.png) Founded by survivors and caregivers of those impacted by _RET_-driven cancers, [RETpositive](https://www.retpositive.org/) aims to build hope, resources and a sense of community for _RET_-positive cancer patients. By sharing emotional support and knowledge of the latest treatment options and current RET specific research, RETpositive hopes to increase both quality of life and life expectancy for those impacted by _RET_-driven malignancies. ![Thanc Foundation logo](https://retevmo.lilly.com/assets/img/logo-thanc.png) The [THANC (Thyroid, Head and Neck Cancer) Foundation](https://thancfoundation.org/) is an international, independent nonprofit dedicated to supporting research and education in the early detection and treatment of thyroid, head and neck cancers. THANC is actively committed to advancing new therapies and alleviating the suffering and functional impairment of patients who undergo treatment. The THANC Guide is a significant resource that endeavors to help patients through their cancer journey. ![ThyCa: Thyroid Cancer Survivors' Association logo](https://retevmo.lilly.com/assets/img/logo-thyca.png) [ThyCa: Thyroid Cancer Survivors’ Association, Inc.](https://www.thyca.org/), an international nonprofit organization advised by thyroid cancer specialists, educates and supports patients and families through its comprehensive website, support groups, person-to-person support, free newsletter and downloadable handbooks and low-iodine cookbook, available in numerous languages. ThyCa sponsors seminars, workshops, and an annual international 3-day conference, as well as Thyroid Cancer Awareness Month, year-round awareness programs for early detection, and thyroid cancer research funds and research grants. ‡This information has been provided by the listed organizations, and Lilly is not responsible for the content. Its use on this site is not intended to serve as an endorsement of the listed organizations. All third-party organization names and other trademarks are the property of their respective trademark owners. Those trademark owners are not affiliated with Lilly and they do not sponsor or endorse this material. Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo Sitemap [Skip to main content](https://retevmo.lilly.com/sitemap#maincontent) # Retevmo Sitemap ## For Patients [For Patients Home](https://retevmo.lilly.com/) - [Understanding Biomarker Testing](https://retevmo.lilly.com/what-is-ret) - [How Retevmo Works](https://retevmo.lilly.com/how-it-works) - [Retevmo in NSCLC](https://retevmo.lilly.com/about-mnsclc) - [Retevmo in Thyroid Cancer](https://retevmo.lilly.com/about-mtc) - [Retevmo in Other Cancers](https://retevmo.lilly.com/other-cancers) - [Taking Retevmo](https://retevmo.lilly.com/taking-retevmo) - [Savings & Support Resources](https://retevmo.lilly.com/savings-support) - [Patient Story](https://retevmo.lilly.com/patient-stories) ## For Healthcare Providers [For Healthcare Providers Home](https://retevmo.lilly.com/hcp) - [About _RET_](https://retevmo.lilly.com/hcp/about-ret) - Efficacy - [_RET_ \+ solid tumors (LIBRETTO-001: Phase I/II)](https://retevmo.lilly.com/hcp/efficacy/libretto-001) - [_RET_ \+ mNSCLC (LIBRETTO-431: Phase III)](https://retevmo.lilly.com/hcp/efficacy/libretto-431) - [_RET_ \+ mMTC (LIBRETTO-531: Phase III)](https://retevmo.lilly.com/hcp/efficacy/libretto-531) - [Safety & Tolerability](https://retevmo.lilly.com/hcp/safety) - [Dosing](https://retevmo.lilly.com/hcp/dosing) - [Testing for _RET_](https://retevmo.lilly.com/hcp/testing) - [Savings & Support](https://retevmo.lilly.com/hcp/savings-support) Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Taking Retevmo [Skip to main content](https://retevmo.lilly.com/taking-retevmo#maincontent) # Taking Retevmo Retevmo is taken by itself and not in combination with additional cancer therapies ![Taking Retevmo](https://retevmo.lilly.com/assets/img/dtc-header_taking_retevmo.jpg) ## **Retevmo** ® Now in tablet form with four dose strengths. [Learn More](https://retevmo.lilly.com/assets/pdf/retevmo-dtc-digital-patient-flyer.pdf) ## How to take Retevmo ![Twice daily dosing icon](https://retevmo.lilly.com/assets/img/icon-dosing-twice-daily.png) Retevmo is taken orally twice daily, with each dose 12 hours apart. ![dosing tablet icon](https://retevmo.lilly.com/assets/img/icon-dosing-two-tablets.jpg) Swallow Retevmo whole. Do not break, chew, or crush. Do not give Retevmo capsules to children if they are unable to swallow capsules. ## Common questions about how to take Retevmo ### Collapse accordion How often should I take Retevmo? Take Retevmo exactly as your doctor tells you. Your doctor may change your dose, if needed. Do not change your dose or stop taking Retevmo without talking to your doctor. ### Collapse accordion If I'm taking other medicines, do these medicines affect how I take Retevmo? \*If you take: - **a proton-pump inhibitor** (PPIs such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole), take Retevmo with food - **an H2 blocker** (such as famotidine, nizatidine, and cimetidine), take Retevmo 2 hours before or 10 hours after taking the H2 blocker - **an antacid** that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take Retevmo 2 hours before or 2 hours after taking the antacid ### Collapse accordion What should I do if I miss a dose or get sick after taking a dose? Do not take a missed dose of Retevmo unless it is more than 6 hours until your next scheduled dose. If you get sick after taking a dose, do not take an extra dose, and take your next dose at your regular time. In the event that you take too much Retevmo, call your doctor or go to the nearest hospital emergency room right away. If you have questions about Retevmo or need more information on how to take it, you should talk to your doctor. You can also call Lilly Support Services™ at 1-800-LillyRx (1-800-545-5979). ## Some possible side effects with Retevmo Retevmo may cause serious side effects, including: - liver problems - lung problems - high blood pressure (hypertension) - heart rhythm changes (QT prolongation) - bleeding problems - allergic reactions - tumor lysis syndrome - risk of wound healing problems - low levels of thyroid hormone (hypothyroidism) - risk to unborn babies - hip joint problems in children Common side effects in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - abdominal pain - constipation - rash - nausea - headache Common side effects in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding The most common severe abnormal laboratory test results in adults include: - lower white blood cell count - higher levels of liver enzymes - lower sodium levels in the blood - lower calcium levels in the blood The most common severe abnormal laboratory test results in children 2 years and older: - decreased levels of calcium in the blood - decreased red blood cell count - decreased white blood cell count. Retevmo may affect fertility in females and males, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you. ![Doctor with side effects clipboard](https://retevmo.lilly.com/assets/img/side-effects-doctor-clipboard-desktop.png) In one clinical trial, _some_ people stopped taking Retevmo due to side effects. Adverse reactions resulting in permanently stopping Retevmo in some patients included: - increased liver enzymes - tiredness - serious infection (sepsis) Side effects requiring dosage interruption or a lowered dose in some of patients included: - increased liver enzymes - diarrhea - heart rhythm changes (QT prolongation) - tiredness - allergic reactions swelling of the arms, legs, hands, and feet (edema) - high blood pressure (hypertension) ![Retevmo patient talking about side effects](https://retevmo.lilly.com/assets/img/dtc-side_effects_bottom.jpg) These are not all of the possible side effects of Retevmo. If you experience side effects while on treatment, it is important that you speak with your doctor or pharmacist. You are encouraged to report side effects of prescription drugs to the FDA. Visit [www.fda.gov/medwatch](http://www.fda.gov/medwatch) or call 1-800-FDA-1088. You may also report side effects to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979). You should avoid taking St. John’s wort, proton-pump inhibitors (PPIs such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, rabeprazole), H2 blockers (such as famotidine, nizatidine, and cimetidine), and antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines during treatment with Retevmo. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work, and other medicines may affect how RETEVMO works, and may increase your risk of side effects. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. If you're taking or about to start taking Retevmo, [learn more about Retevmo Savings and Support](https://retevmo.lilly.com/savings-support) Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Biomarker Testing Overview [Skip to main content](https://retevmo.lilly.com/what-is-ret#maincontent) # Understanding Biomarker Testing Biomarker testing can help you and your doctor find the right treatment option for you ![Doctor explaning biomarker testing to patient](https://retevmo.lilly.com/assets/img/dtc-hero-understanding_biomarker_testing.jpg) ![DNA icon](https://retevmo.lilly.com/assets/img/dtc-icon-testing.png) ## Biomarker testing allows your healthcare team to understand more about your cancer Your cancer may be driven by a genomic alteration, or a change, in your cancer’s DNA. A genomic alteration means that the genes in some of your cells have changed and may be abnormal. If your cancer is driven by a genomic alteration, there may be additional treatment options available to you. To determine if your cancer is being driven by an alteration, your doctor will need to order a biomarker test. Biomarker testing is used to detect any possible genomic alterations in your cancer’s DNA. It's important for your doctor to order a biomarker test to know if your cancer is being driven by an alteration like _EGFR_, _ALK_, _KRAS_, or _RET_. ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; KRAS=Kirsten rat sarcoma; RET=rearranged during transfection. ![nsclc patient](https://retevmo.lilly.com/assets/img/dtc-lung_patient.jpg) Approximately 69% of people living with lung cancer have a genomic alteration that may be treatable, according to a review of published clinical studies. ![Thyroid patients](https://retevmo.lilly.com/assets/img/dtc-thyroid_patients.jpg) While the number of genomic alterations to test for in thyroid cancers is small, _RET_ alterations are relatively common in medullary thyroid cancer (MTC) and other advanced or metastatic thyroid cancers. ## What is _RET_? _RET_ is a gene that everyone has, but certain cancers can be driven by alterations in _RET_ There are different genomic alterations that may be driving your cancer. An alteration may occur in a gene called _RET_ (rearranged during transfection). If you test positive for a _RET_ alteration, it means _RET_ is likely driving the growth of your tumor. There are effective therapies that target this specific alteration. Knowing if a _RET_ alteration is driving your cancer can help you and your doctor choose the right treatment for you. Retevmo is available for _RET_-positive advanced non-small cell lung cancer (NSCLC), thyroid cancers, and certain other cancers [See how Retevmo works](https://retevmo.lilly.com/how-it-works) **SELECT SAFETY INFORMATION** **RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your doctor will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your doctor right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area ## Talk to your doctor about biomarker testing to find out if Retevmo is a treatment option for you ![step 1, ask doctor icon](https://retevmo.lilly.com/assets/img/dtc-testing_step_01.png) Ask your doctor if you have received a broad biomarker test for less common alterations like _RET_. ![step 2 - talk to doctor about results icon](https://retevmo.lilly.com/assets/img/dtc-testing_step_02.png) Talk to your doctor about the results of the biomarker test. ![dosing tablet 3 icon](https://retevmo.lilly.com/assets/img/dtc-testing_step_03.svg) Treatment with Retevmo may be an option if your NSCLC, thyroid cancer, or other cancer tests positive for _RET_. Certain biomarker tests require your doctor to biopsy the tumor, which means removing some tissue or blood for testing. Some biopsies are surgical, may require sedation, and come with a risk of infection. Your doctor will select the right type of biopsy for your tumor. If your tumor has been biopsied previously, some tissue may already be available for testing. ## Here are a few questions to help you talk to your doctor **Quotes** **Have I been tested for all biomarkers that have available** **treatments?** **Quotes** Ask your doctor if they recommend a broad biomarker test that can show if you have a less common alteration like _RET_. The sooner it is determined whether your NSCLC, thyroid cancer, or other cancer is _RET_-positive, the sooner you and your doctor can determine if Retevmo is right for you. **Quotes** **What does it mean to test positive for** **_RET_?** **Quotes** If your tumor tests positive for _RET_, this means _RET_ may be what is driving your cancer. **Quotes** **What does it mean if I have _RET_-positive medullary thyroid** **cancer?** **Quotes** People with medullary thyroid cancer (MTC) may find that their cancer is hereditary, which means there is a chance their family members could have the same diagnosis. If you have hereditary MTC, talk to your doctor about how best to discuss your diagnosis with your family. ![Frequently asked questions](https://retevmo.lilly.com/assets/img/dtc-faq.png) [Retevmo in NSCLC](https://retevmo.lilly.com/about-mnsclc) See how Retevmo may help people living with _RET_-positive advanced NSCLC [Retevmo in thyroid cancer](https://retevmo.lilly.com/about-mtc) See how Retevmo may help people living with _RET_-positive advanced thyroid cancer [Retevmo in other cancers](https://retevmo.lilly.com/other-cancers) See how Retevmo may help people living with certain other _RET_-positive advanced cancers Important Safety Information and Indication or Indications. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** INDICATIONS AND SAFETY SUMMARY Important Safety Information and Indication or Indications. Select to Expand. Important Safety Information. Select to Expand. Warnings **\- RETEVMO may cause serious side effects, including:** Important Safety Information. Select to Expand. ## Warnings **\- RETEVMO may cause serious side effects, including:** **Liver problems:** Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: - yellowing of your skin or the white part of your eyes (jaundice) - dark, “tea-colored” urine - sleepiness - bleeding or bruising - loss of appetite - nausea or vomiting - pain on the upper right side of your stomach area **Lung problems:** RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: - shortness of breath - cough - fever **High blood pressure (hypertension):** High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: - confusion - headaches - shortness of breath - dizziness - chest pain **Heart rhythm changes (QT prolongation).** RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroid-stimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: - loss of consciousness - fainting - dizziness - a change in the way your heart beats (heart palpitations) **Bleeding problems:** RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: - vomiting blood or if your vomit looks like coffee-grounds - pink or brown urine - red or black stools that look like tar - coughing up blood or blood clots - unusual bleeding or bruising of your skin - menstrual bleeding that is heavier than normal - unusual vaginal bleeding - nose bleeds that happen often - drowsiness or difficulty being awakened - confusion - headache - change in speech **Allergic reactions:** RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. **Tumor lysis syndrome (TLS):** TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: - nausea - vomiting - weakness - swelling - shortness of breath - muscle cramps - seizures **Risk of wound healing problems:** Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. - You should stop taking RETEVMO at least 7 days before planned surgery. - Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. **Low thyroid hormone levels in your blood (hypothyroidism).** Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: - weight gain - feeling cold - tiredness that worsens or does not go away - constipation **Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children.** Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. **Common side effects** The most common side effects of RETEVMO in adults with solid tumors include: - swelling of your arms, legs, hands, and feet (edema) - diarrhea - tiredness - dry mouth - stomach-area (abdominal) pain - constipation - rash - nausea - headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: - muscle and bone pain - diarrhea - headache - nausea - vomiting - coronavirus infection - stomach-area (abdominal) pain - tiredness - fever - bleeding **The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include** decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. **The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include** decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. - RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. - **If you are able to become pregnant:** - Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. - You should use effective birth control (contraception) during treatment and for **1 week** after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. - Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. - **Males with partners who are able to become pregnant** should use effective birth control during treatment with RETEVMO and for **1 week** after your last dose of RETEVMO. **These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [**www.fda.gov/medwatch**](http://www.fda.gov/medwatch).** #### **Before using** Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: - have liver problems - have lung or breathing problems other than lung cancer - have high blood pressure - have heart problems, including a condition called QT prolongation - have bleeding problems - plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. - are pregnant or plan to become pregnant. See section above for additional information. - are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. **Also tell your healthcare provider about all the medicines you take**, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. - During treatment with RETEVMO, you should avoid taking: - St. John’s wort, - proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, - H2 blockers such as famotidine, nizatidine, and cimetidine, - antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. #### **How to take RETEVMO** - Take RETEVMO exactly as your healthcare provider tells you. - Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. - Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. - Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. - Take RETEVMO with or without food. - If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. - Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. - If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. #### **How to take RETEVMO with certain other medicines** - If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. - If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. - If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. #### **Learn more** RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](https://retevmo.lilly.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 RETEVMO® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Indication or Indications. Select to Expand. INDICATIONS AND SAFETY SUMMARY Indication or Indications. Select to Expand. ## INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal _RET_ genes in: - adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. - adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). - adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. - adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. - It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: - advanced MTC or MTC that has spread who require a medicine by mouth or injection. - advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. - locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. - in children for other conditions. \* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. ## Retevmo for RET-driven cancers [Skip to main content](https://retevmo.lilly.com/hcp/about-ret#maincontent) # Retevmo was designed to target _RET_, the primary driver of certain _RET_-driven cancers1,2 Much like what has been achieved for patients with _EGFR_, _ALK_, _ROS1_, _NTRK_, and _BRAF_ alterations, Retevmo expands treatment options for patients with certain _RET_-driven cancers1-4 _RET_ alterations are a primary driver of tumor growth in the following tumor types2: ![Role of RET for RET-driven cancers such as RET fusions and RET point mutations](https://retevmo.lilly.com/assets/img/0279-ret-prevalence-list-desktop-new.png) Up View Description In _RET_-driven cancers, the prevalence of _RET_ fusions is <2% in NSCLC, <10% in papillary thyroid cancer, and <1% of other solid tumors (including pancreatic, colorectal, sarcoma, ovarian, breast, and salivary). The prevalence of _RET_ point mutations in medullary thyroid cancer (MTC) is >60% in sporadic MTC and 98% in germline MTC. - _RET_ point mutations may be present in other tumors but are believed to only drive medullary thyroid cancer (MTC)7-9 Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious.1 **_RET_ driver alterations are predominantly mutually exclusive from other oncogenic drivers2** Most actionable genomic alterations are uncommon, highlighting the need for broad molecular profiling10,11 [Curious about _RET_ testing?](https://retevmo.lilly.com/hcp/testing) **Select Important Safety Information** **Hepatotoxicity**: Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. ## Retevmo demonstrated highly selective and potent RET inhibition1,12,13 Retevmo inhibited wild-type RET and multiple mutated RET isoforms, and was 250 times more selective for RET than 98% of ~300 kinases tested in preclinical studies1,14 Retevmo also inhibited certain isoforms of VEGFR and FGFR at higher concentrations that were still clinically achievable. In comparison, Retevmo inhibited RET at ~60-fold lower concentrations than FGFR1 and 2 and at ~8-fold lower concentrations than VEGFR3 in preclinical studies.1 Therapeutic Kinase Activity by Selectivity1,15,16 ![Retevmo was 250 times more selective for RET than 98% of ~300 kinases tested](https://retevmo.lilly.com/assets/img/ret-kinome-tree.svg) Illustration reproduced courtesy of Cell Signaling Technology, Inc. ( [www.cellsignal.com](https://www.cellsignal.com/)). The above depicts the human kinome, which is a map of the 518 protein kinases that compose 1.7% of all human genes. The circles indicate the positions of specific kinase targets.17,18 Retevmo demonstrated potency based on phase I dose escalation data showing >90% inhibition of RET wild type and RET M918T at recommended dose.13 Retevmo was designed to selectively target an anticipated acquired resistance mechanism (V804M gatekeeper).1,2,12 Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious.1 **Retevmo crossed the blood-brain barrier and showed anti-tumor activity in mice intracranially implanted with a patient-derived _RET_ fusion-positive tumor.1,12** ALK=anaplastic lymphoma kinase; BRAF=v-raf murine sarcoma viral oncogene homolog B; EGFR=epidermal growth factor receptor; FGFR=fibroblast growth factor receptor; MTC=medullary thyroid cancer; NSCLC=non-small cell lung cancer; NTRK=neurotrophic receptor tyrosine kinase; PTC=papillary thyroid cancer; RET=rearranged during transfection; ROS1=reactive oxygen species 1; VEGFR=vascular endothelial growth factor receptor. **References: 1.** Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. **2.** Drilon A, Hu ZI, Lai GGY, et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. _Nat Rev Clin Oncol_. 2018;15(3):151-167. **3**. Amatu A, Sartore-Bianchi A, Siena S. _NTRK_ gene fusions as novel targets of cancer therapy across multiple tumour types. _ESMO Open_. 2016;1(2):e000023. doi:10.1136/esmoopen-2015-000023. **4.** Ferrara R, Auger N, Auclin E, et al. Clinical and translational implications of _RET_ rearrangements in non-small cell lung cancer. _J Thorac Oncol_. 2018;13(1):27-45. **5.** Yang SR, Aypar U, Rosen EY, et al. A performance comparison of commonly used assays to detect RET fusions. _Clin Cancer Res._ 2021;27(5):1316-1328. **6.** Elisei R, Tacito A, Ramone T, et al. Twenty-five years experience on RET genetic screening on hereditary MTC: an update on the prevalence of germline RET mutations. _Genes (Basel)_. 2019;10(9). doi:10.3390/genes10090698. **7.** Mulligan LM. GDNF and the RET receptor in cancer: new insights and therapeutic potential. _Front Physiol_. 2019;9:1873. **8.** Mulligan LM. RET revisited: expanding the oncogenic portfolio. _Nat Rev Cancer_ 2014;14(3):173-186. **9.** Kato S, Subbiah V, Marchlik E, et al. _RET_ aberrations in diverse cancers: next-generation sequencing of 4,871 patients. _Clin Cancer Res_. 2017;23(8):1988-1997. **10.** Hirsch FR, Suda K, Wiens J, et al. New and emerging targeted treatments in advanced non-small-cell lung cancer. _Lancet_. 2016;388(10048):1012-1024. **11.** Suh JH, Johnson A, Albacker L, et al. Comprehensive genomic profiling facilitates implementation of the National Comprehensive Cancer Network Guidelines for lung cancer biomarker testing and identifies patients who may benefit from enrollment in mechanism-driven clinical trials. _Oncologist_. 2016;21(6):684-691. **12.** Subbiah V, Velcheti V, Tuch BB, et al. Selective RET kinase inhibition for patients with _RET_-altered cancers. _Ann Oncol_. 2018;29(8):1869-1876. **13.** Drilon A, Subbiah V, Oxnard G, et al. LIBRETTO-001: A phase 1 study of LOXO-292, a potent and highly selective RET inhibitor, in patients with _RET_-altered cancers. Oral presentation at: American Society of Clinical Oncology Annual Meeting. June 1–5, 2018; Chicago, IL. **14.** Data on File, Lilly USA, LLC, DOF-SE-US-0004. **15.** DuBois SG, Albert CM, Mascarenhas L, et al. A phase 1 study of LOXO-292, a highly selective RET inhibitor, in pediatric patients with _RET_-altered cancers. Poster presented at: 2019 ASCO Annual Meeting; June 1, 2019; Chicago, Illinois. Abstract TPS10066. **16.** Uitdehaag JCM, Verkaar F, Alwan H, et al. A guide to picking the most selective kinase inhibitor tool compounds for pharmacological validation of drug targets. _Br J Pharmacol_. 2012;166(3):858-876. **17.** Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome. _Science_. 2002;298(5600):1912-1934. **18.** Chartier M, Chénard T, Barker J, et al. Kinome Render: a stand-alone and web-accessible tool to annotate the human protein kinome tree. _PeerJ_. 2013;1:e126. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Retevmo Dosing Information [Skip to main content](https://retevmo.lilly.com/hcp/dosing#maincontent) # Retevmo recommended dosing and administration Patient selection for treatment with Retevmo should be based on the presence of a _RET_ gene fusion (NSCLC, thyroid cancer, or solid tumors) or specific _RET_ gene mutation (MTC) in tumor specimens. Information on FDA-approved test(s) for the detection of _RET_ gene fusions and _RET_ gene mutations is available at: [http://www.fda.gov/CompanionDiagnostics](http://www.fda.gov/CompanionDiagnostics). An FDA-approved companion diagnostic test for the detection of _RET_ gene fusions and _RET_ gene mutations in plasma is not currently available. ![Chart showing recommended Retevmo dosages.](https://retevmo.lilly.com/assets/img/c-se-us-0077-retevmo-dosing-new-template-all-indications-with-peds-desktop.png) Up View Description Chart showing the recommended dosing for Retevmo. Adult and pediatric patients 12 years and older should be dosed based on body weight. Patients weighing less than 50 kg, take 120 mg twice daily. Patients weighing 50 kg or greater, take 160 mg twice daily. Pediatric patients 2 years to less than 12 years of age should be dosed based on body surface area. Patients with a body surface area of 0.33 to 0.65 m2, take 40 mg three times daily. Patients with a body surface area of 0.66 to 1.08 m2, take 80 mg twice daily. Patients with a body surface area of 1.09 to 1.52 m2, take 120 mg twice daily. Patients with a body surface area of greater than or equal to 1.53 m2, take 160 mg twice daily. - Retevmo may be taken with or without food. When administered with a proton pump inhibitor (PPI), take with food. - Instruct patients to swallow Retevmo whole. Do not break, crush or chew. Do not administer to pediatric patients who are unable to swallow a capsule. - Do not take a missed dose unless it is more than 6 hours until next scheduled dose. - If vomiting occurs after Retevmo administration, do not administer an additional dose, and continue to the next scheduled time for the next dose. ## Recommended dose reductions due to adverse reactions (ARs)1 ![dose reduction reference chart](https://retevmo.lilly.com/assets/img/c-se-us-0076-se-hcp-pay-all-retevmo-dose-reductions-for-adverse-reactions_desktop.png) ![additional dose modification chart](https://retevmo.lilly.com/assets/img/c-se-us-0069_se-hcp-pay-dos-additional-dose-modifications-desktop-v3.png) **Reduce the recommended dosage of Retevmo for patients with severe hepatic impairment to 80 mg orally twice daily.** [Find out more about _RET_ diagnostic tests](https://retevmo.lilly.com/hcp/testing) **Select Important Safety Information** **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. ALT=alanine aminotransferase; AST=aspartate aminotransferase; RET=rearranged during transfection. **Reference: 1.** Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Retevmo Safety Information [Skip to main content](https://retevmo.lilly.com/hcp/safety#maincontent) # Retevmo safety and tolerability were evaluated in 796 patients1 Adverse Reactions (ARs) (≥20%) in Patients Who Received Retevmo in LIBRETTO-0011 ![Adverse reactions in LIBRETTO-001 Trial](https://retevmo.lilly.com/assets/img/c-se-us-0018-se-hcp-pay-saf-safety-adverse-reactions3.png) Up View Description **Adverse Reactions (≥20%) in Patients Who Received Retevmo (N=796) in LIBRETTO-001 were Gastrointestinal: Dry Mouth:** 43% Grades 1-4, 0% Grades 3-4; **Diarrhea:** 47% Grades 1-4, 5% Grades 3-4; **Constipation:** 33% Grades 1-4, 0.8% Grades 3-4; **Nausea:** 31% Grades 1-4, 1.1% Grades 3-4; **Abdominal Pain:** 34% Grades 1-4, 2.5% Grades 3-4; **Vomiting:** 22% Grades 1-4, 1.8% Grades 3-4; **Vascular: Hypertension:** 41% Grades 1-4, 20% Grades 3-4; **General: Fatigue:** 46% Grades 1-4, 3.1% Grades 3-4; **Edema:** 49% Grades 1-4, 0.8% Grades 3-4; **Arthralgia:** 21% Grades 1-4, 0.3% Grades 3-4; **Skin: Rash:** 33% Grades 1-4, 0.6% Grades 3-4; **Nervous System: Headache:** 28% Grades 1-4; 1.4% Grades 3-4; **Respiratory: Cough:** 24% Grades 1-4, 0% Grades 3-4; **Dyspnea:** 22% Grades 1-4, 3.1% Grades 3-4; **Investigations: Prolonged QT Interval:** 21% Grades 1-4, 4.8% Grades 3-4; and **Blood and Lymphatic System: Hemorrhage:** 22% Grades 1-4, 2.6% Grades 3-41 \*Only includes a grade 3 adverse reaction #Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 Laboratory Abnormalities (≥20%) Worsening from Baseline in Patients Who Received Retevmo in LIBRETTO-0011 ![Laboratory abnormalities in LIBRETTO-001 Trial](https://retevmo.lilly.com/assets/img/c-se-us-0018-se-hcp-pay-saf-safety-adverse-reactions5.png) Up View Description **Laboratory Abnormalities (≥20%) Worsening from Baseline in Patients Who Received Retevmo in LIBRETTO-001 were Gastrointestinal: Increased AST:** 59% Grades 1-4, 11% Grades 3-4; **Increased ALT:** 56% Grades 1-4, 12% Grades 3-4; **Increased Glucose:** 53% Grades 1-4, 2.8% Grades 3-4; **Decreased Albumin:** 56% Grades 1-4, 2.3% Grades 3-4; **Decreased Calcium:** 59% Grades 1-4, 5.7% Grades 3-4; **Increased Creatinine:** 47% Grades 1-4, 2.4% Grades 3-4; **Increased Alkaline Phosphatase:** 40% Grades 1-4, 3.4% Grades 3-4; **Increased Total Cholesterol:** 35% Grades 1-4, 1.7% Grades 3-4; **Decreased Sodium:** 42% Grades 1-4, 11% Grades 3-4; **Decreased Magnesium:** 33% Grades 1-4, 0.6% Grades 3-4; **Increased Potassium:** 34% Grades 1-4, 2.7% Grades 3-4; **Increased Bilirubin:** 30% Grades 1-4, 2.8% Grades 3-4; **Decreased Glucose:** 34% Grades 1-4, 1.0% Grades 3-4; **Hematology: Decreased Platelets:** 37% Grades 1-4, 3.2% Grades 3-4; **Decreased Lymphocytes:** 52% Grades 1-4, 20% Grades 3-4; **Decreased Hemoglobin:** 28% Grades 1-4, 3.5% Grades 3-4; **Decreased Neutrophils:** 25% Grades 1-4, 3.2% Grades 3-41 aDenominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available, which ranged from 765 to 791 patients. #Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 - Dose interruptions and dose reductions due to ARs occurred in 64% and 41% of patients who received Retevmo, respectively.1 - ARs requiring dosage interruption in ≥5% of patients included increased ALT, increased AST, diarrhea, and hypertension.1 - ARs requiring dosage reductions in ≥2% of patients included increased ALT, increased AST, QT prolongation, fatigue, diarrhea, drug hypersensitivity, and edema.1 - Clinically relevant ARs in ≤15% of patients who received Retevmo include hypothyroidism (13%); pneumonia (11%), hypersensitivity (6%); interstitial lung disease/pneumonitis, chylothorax, chylous ascites, or tumor lysis syndrome (all <2%).1 Due to rounding and potential double-counting of patients, percentages presented may not add up to the indicated totals. See full Prescribing Information for more information on adverse reactions, laboratory abnormalities, and dose modifications. **8% (n=64) of patients permanently discontinued Retevmo (N=796) due to adverse reactions. 3% (n=25) were considered treatment-related, as assessed by trial investigator. Adverse reactions resulting in permanent discontinuation in ≥0.5% of patients included increased ALT (0.6%), fatigue (0.6%), sepsis (0.5%), and increased AST (0.5%).1,2** [See dosing for Retevmo](https://retevmo.lilly.com/hcp/dosing) ALT=alanine aminotransferase; AST=aspartate aminotransferase. **References: 1.** Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. **2.** Data on File, Lilly USA, LLC, DOF-SE-US-0060. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Retevmo Savings Support [Skip to main content](https://retevmo.lilly.com/hcp/savings-support#maincontent) Information To continue using a Savings Card in 2025, eligible patients can download now under the [Savings & Support Page](https://retevmo.lilly.com/hcp/savings-support). # Savings & Support ## Support tailored to your eligible patient’s Retevmo treatment journey\* [Enroll your patients (PDF)](https://retevmo.lilly.com/assets/pdf/retevmo_interactivefilled.pdf) To enroll your eligible patients in all or any of these support programs\*, please visit retevmo.lilly.com, or call Lilly Support Services™ at 1-800-LillyRx (1-800-545-5979), Monday through Friday between 8 AM and 10 PM ET. ![Retevmo savings card](https://retevmo.lilly.com/assets/img/icon-savings-card.png) **Retevmo Savings Card** Eligible commercially insured covered patients pay as little as $0 a month.† †Month is defined as 30 days [Download Savings Card](https://retevmo.lilly.com/hcp/savings-support#) Questions about savings? Call the Retevmo Savings Card Support Line at 1-866-615-3716. By enrolling in and using the Retevmo Savings Card Program (“Program”) and using the Retevmo Savings Card (“Card”), you attest that you meet the eligibility criteria, and you agree to comply with the terms and conditions described below: **Card Eligibility:** 1. You have been prescribed Retevmo® (selpercatinib) for an approved use consistent with FDA-approved product labeling; 2. You are enrolled in a commercial drug insurance plan and have coverage for Retevmo: 3. **You are not enrolled in any state, federal, or government funded healthcare program, including, without limitation, Medicaid, Medicare, Medicare Part D, Medicare Advantage, Medigap, DoD, VA, TRICARE®/CHAMPUS, or any state prescription drug assistance program;** 4. You are a resident of the United States or Puerto Rico; and 5. You are 18 years of age or older. **Card Terms and Conditions** For patients with commercial drug insurance coverage for Retevmo: You must have commercial drug insurance that covers Retevmo and a prescription for an approved use consistent with FDA-approved product labeling to pay as little as $0 for a 1-month prescription fill of Retevmo. Month is defined as 30-days. Card savings are subject to a maximum monthly savings of wholesale acquisition cost plus usual and customary pharmacy charges and separate maximum annual savings of up to $9,200 per calendar year. Card may be used for a maximum of up to 14 prescription fills per calendar year. Except where prohibited by applicable state law, Card monthly and annual savings are reduced if Lilly identifies that you are enrolled in a plan or program, sometimes called a maximizer plan, that adjusts your cost sharing amount to be equal to or include some portion of the savings provided by the Card and attempts to prevent the savings from this Card from being applied to your out-of-pocket costs, including but not limited to copayments, coinsurances, and deductibles (“Maximizer”). If the Program identifies you are enrolled in a Maximizer, Card savings are reduced to a maximum monthly savings of up to $25 and a separate maximum annual savings of up to $350 per calendar year. If you have reason to believe that the Program erroneously identified enrollment in a Maximizer, please call the Retevmo Savings Card Program at 1-866-615-3716. Subject to Lilly USA, LLC’s (“Lilly”) right to terminate, rescind, revoke, or amend Card eligibility criteria and/or Card terms and conditions which may occur at Lilly’s sole discretion, without notice, and for any reason. Card expires and savings end on 12/31/2025. **Additional Program Terms and Conditions** If you have an insurance plan that is participating in an alternate funding program (“AFP”) that requires you to apply to the Retevmo Savings Card Program or otherwise pursue specialty drug prescription coverage through an alternate funding vendor as a condition of, requirement for, or prerequisite to coverage of Retevmo, you are not eligible for and are prohibited from using the Retevmo Savings Card Program. AFPs include programs where coverage, reimbursement, or patient out of pocket costs for a product in some way vary based on the availability of a manufacturer co-pay program. AFPs may modify, delay, deny, restrict, or withhold insurance benefits or coverage from patients, or exclude Lilly products from coverage contingent upon a member’s use of Retevmo Savings Card Program. You agree to inform the Retevmo Savings Card Program if you are or become a member of such an alternative funding program. You are responsible for any applicable taxes, fees, and any amount that exceeds the monthly or annual maximum Card savings. Monthly and annual maximum savings are set at Lilly’s sole and absolute discretion and may be changed with or without notice at any time for any reason. At its sole discretion and with or without notice, Lilly may reduce, eliminate, or otherwise modify the Card savings for any reason, including but not limited to if your commercial drug insurance plan imposes additional requirements which limits or prevents you from receiving coverage for Retevmo, only allows partial coverage for Retevmo, removes coverage for Retevmo and requires you to utilize the Card, does not provide a material level of financial assistance for the cost of Retevmo, or does not apply Card payments to satisfy your co-payment, deductible, or coinsurance for Retevmo. Card savings are not valid for: Massachusetts residents if an AB-rated generic equivalent is available; California residents if an FDA-approved therapeutic equivalent is available. You must meet the Card eligibility criteria, terms and conditions every time you use the Card. If at any time you begin receiving drug coverage under any state, federal, or government funded healthcare program, you understand that you will no longer be eligible for the Retevmo Savings Card and agree to call the Retevmo Savings Card Program at 1-866-615-3716 to stop participation. Card activation is required. You may not seek reimbursement from your health insurance, any third party, or any health savings, flexible spending, or other healthcare reimbursement accounts, for any amount of the savings received through the Card. By utilizing the Card, you agree that if you are required to do so under the terms of your insurance coverage for this prescription or are otherwise required to do so by law, you will notify your Insurance Carrier of your redemption of the Card. Card savings cannot be combined or utilized with any other program, discount, discount card, cash discount card, coupon, incentive, or similar offer involving Retevmo. You agree that this Card savings is intended solely for the benefit of you, the patient, and that the Card benefits are nontransferable. It is prohibited for any person to sell, purchase, or trade; or to offer to sell, purchase, or trade, or to counterfeit the Card. **THIS CARD IS NOT INSURANCE**. Lilly has the sole right to interpret and apply Card eligibility criteria, and terms and conditions. Card eligibility, and terms and conditions may be terminated, rescinded, revoked, or amended by Lilly at any time without notice and for any reason. Lilly’s sole discretion to terminate, rescind, revoke, or amend Card eligibility and/or Card terms and conditions includes the right to terminate any individual Card if Lilly determines, in its sole discretion, that a patient does not satisfy the Card’s eligibility criteria or is using or has attempted to use the Card inconsistently with these terms and conditions. Eligibility criteria, and terms and conditions for the Retevmo Savings Card Program may change from time to time; the most current version can be found at [https://retevmo.lilly.com/savings-support](https://retevmo.lilly.com/savings-support). You may be required to obtain a new Card, including if any Card terms and conditions have been terminated, rescinded, revoked, or amended by Lilly. Card void where prohibited by law. Subject to Lilly’s right to terminate, rescind, revoke or amend Card eligibility criteria and/or Card terms and conditions which may occur at Lilly’s sole discretion, without notice, and for any reason. Card expires and savings end on 12/31/2025. TRICARE® is a registered trademark of the Department of Defense (DoD), DHA. ![Retevmo myRightDose exchange program](https://retevmo.lilly.com/assets/img/icon-dose-exchange.png) **MyRightDose: A Dose Exchange Program‡** May simplify midcycle dose changes for patients—MyRightDose ships the appropriate dose directly to your patient’s home in as early as 48 hours and at no cost to the patient. ‡Additional terms and conditions apply. See the [MyRightDose enrollment form (PDF)](https://retevmo.lilly.com/assets/pdf/dose-exchange-enrollment-form.pdf) for details. ![Insurance and coverage assistance](https://retevmo.lilly.com/assets/img/icon-expertise.png) **Insurance and Coverage Assistance\*** Benefits investigation - Helps eligible enrolled patients understand their coverage options, locate the appropriate specialty pharmacy, and identify their lowest possible out-of-pocket cost Field reimbursement manager - Helps patients access prescribed Lilly FDA-approved medicines ![Retevmo Digital Starter Kit](https://retevmo.lilly.com/assets/img/hcp-mobile-phone.png) **Retevmo Digital Starter Kit** The Retevmo Digital Starter Kit provides patients with key information and savings opportunities. Have patients text the following for more information: **RETL** to **85099** for Retevmo NSCLC resources **RETT** to **85099** for Retevmo thyroid cancer resources \*Lilly Support Services™ for Retevmo® programs and offerings are not a guarantee of coverage. Terms and conditions apply for all programs. See enrollment form for details. ## Access Resources Retevmo is available through: ![Specialty pharmacy](https://retevmo.lilly.com/assets/img/icon-speciality-pharmacy.png) Contracted specialty pharmacies§ ![Your hospital](https://retevmo.lilly.com/assets/img/icon-hospital-health-system.png) Hospital and health system practices ![Talking to your doctor](https://retevmo.lilly.com/assets/img/icon-in-office-dispensing.png) In-office dispensing practices (IODs) Retevmo is available through contracted specialty pharmacies and can be purchased through authorized distributors. [See a list of specialty pharmacies (PDF)](https://retevmo.lilly.com/assets/pdf/specialty-pharmacies-list.pdf) §Eligible pharmacies can purchase Retevmo through authorized distribution partners. A list of authorized distributors can be found at [lillytrade.com](https://www.lillytrade.com/). **Here are some helpful resources to help you and your patients with common access issues** ![Access, reimbursement and distribution guide](https://retevmo.lilly.com/assets/img/icon-access-guide.png) Retevmo access, reimbursement, and distribution The access and reimbursement landscape can be complex and cumbersome. Information within the guide can help you navigate the complexities of the reimbursement landscape. [Download distribution guide (PDF)](https://retevmo.lilly.com/assets/pdf/pp-se-us-1337-access-reimbursement-coding-guide.pdf) ![Appeals letter](https://retevmo.lilly.com/assets/img/icon-appeals-letter.png) Coverage authorization appeals letter If an initial claim or coverage authorization request letter is denied, the payer may require a coverage authorization appeals letter. [Download coverage authorization appeals letter (PDF)](https://retevmo.lilly.com/assets/pdf/retevmo-payer-all-digital-customer-resource-sample-appeals-letter-21Sep22.pdf) ![Letter of medical necessity LMN](https://retevmo.lilly.com/assets/img/icon-letter-of-mn.png) Letter of medical necessity (LMN) Many health plans require that an LMN accompany a coverage authorization appeals letter. [Download letter of medical necessity (LMN) (PDF)](https://retevmo.lilly.com/assets/pdf/retevmo-payer-all-digital-customer-resource-sample-medical-necessity-letter-21Sep22.pdf) ![Retevmo treatment plan guide](https://retevmo.lilly.com/assets/img/icon-plan-guide.png) Treatment plan guide An easy-to-use resource to help the pharmacy develop electronic order sets that are included in electronic health record systems. [Download treatment plan guide (PDF)](https://retevmo.lilly.com/assets/pdf/retevmo-payer-all-digital-customer-resource-treatment-plan-guide-21Sep22.pdf) ![Enrollment form](https://retevmo.lilly.com/assets/img/icon-enrollment-form.png) Enrollment form Enroll your patients to gain access to the Retevmo support offerings. [Download enrollment form (PDF)](https://retevmo.lilly.com/assets/pdf/retevmo_interactivefilled.pdf) Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## RET Testing Guidelines [Skip to main content](https://retevmo.lilly.com/hcp/testing#maincontent) # Testing for _RET_ is essential to identify patients who may be eligible for Retevmo1 ![NCCN recommends testing for RET in eligible patients](https://retevmo.lilly.com/assets/img/hcp-kcd-nccn_rec-test.svg) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for _RET_ alterations in appropriate patients with advanced and/or metastatic NSCLC and thyroid carcinoma\* to determine if they are eligible for _RET_ inhibitors such as selpercatinib (Retevmo)2,3 NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. **Next-generation sequencing (NGS) can be an accurate and tissue-efficient method to test for driver _RET_ alterations and other targetable biomarkers4-7†** Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious.1 - Both _RET_ point mutations and fusions can be detected by NGS.4-6 - Immunohistochemistry (IHC) is not preferred for detecting _RET_ alterations due to low sensitivity and variable specificity9,10 - Test the tissue: molecular testing of FFPE tumor tissue specimens is preferred for detecting _RET_ fusions and point mutations8,11-13 [Discover more about _RET_ alterations](https://retevmo.lilly.com/hcp/about-ret) ![In the LIBRETTO-001 clinical trial, NGS testing was used to identify driver RET alterations in 86% of patients](https://retevmo.lilly.com/assets/img/testing-pie-chart.svg) - In the clinical trial, identification of a _RET_ gene alteration was prospectively determined in local laboratories using NGS, PCR, or FISH1 - **IHC testing was not used in LIBRETTO-0011** ## Why NGS? Broad molecular profiling to identify appropriate targeted therapies can improve outcomes in NSCLC14 - NCCN Guidelines for NSCLC recommend that, when feasible, molecular testing of NSCLC specimens be performed via a broad, panel-based approach, most typically performed by NGS2 - Because of potential tissue limitations in metastatic NSCLC and the increased number of actionable biomarkers, NGS testing is part of the most comprehensive strategy to identify appropriate targeted therapies7 - Consider NGS testing to identify the 69% of patients with lung adenocarcinoma who have a potentially actionable oncogenic driver alteration and may benefit from appropriate approved or investigational targeted therapy15,16 ![NGS testing increased number of potentially actionable biomarkers by more than 50%](https://retevmo.lilly.com/assets/img/69-percent-chart-desktop-v2.png) **Emerging** =biomarkers with therapies under investigation but not approved. **Other** =unknown oncogenic driver detected.16 **_EGFR_** = _EGFR_ sensitizing mutations including exon 20 insertions.16,23 **_EGFR_ other** =secondary _EGFR_ mutations, including Thr790Met and Cys797Ser, and other less common _EGFR_ mutations.16 **_KRAS_ other** =all _KRAS_ mutations other than _KRAS_ G12C.16,22 **NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)** For NSCLC: - recommend testing for _RET_ fusions in eligible patients with metastatic non-small cell lung cancer2 - recommend molecular testing and strongly advise broad molecular profiling for multiple biomarkers, including _RET_, in eligible patients with metastatic NSCLC2\*‡ \*The NCCN Guidelines provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories. †Through design and validation, the test has established high sensitivity, specificity, and reproducibility for the detection of genomic alterations. ‡It is recommended at this time that, when feasible, testing be performed via a broad, panel-based approach, most typically performed by NGS. For patients who, in broad panel testing, don’t have identifiable driver oncogenes (especially in never smokers), consider RNA-based NGS, if not already performed, to maximize detection of fusion events. For Thyroid Carcinoma: - recommend molecular testing for _RET_ fusions and _RET_ point mutations for certain patients with advanced or metastatic thyroid carcinomas3 Consider waiting for _RET_ test results before making therapeutic decisions1 **NGS testing** - NGS testing for _RET_ fusions: when properly designed, NGS testing is able to detect known and unknown fusion events6 - A combination of RNA- and DNA-based NGS testing may be a more comprehensive approach to identify oncogenic drivers missed by DNA-based NGS alone24 * * * Most common _RET_ fusion partners identified in the [LIBRETTO-001 phase I/II clinical trial](https://retevmo.lilly.com/hcp/efficacy/libretto-001?section=trial-design): **NSCLC25:** - 59% KIF5B - 22% CCDC6 - 11% Unknown§ - 6% Otherǁ - 2% NCOA4 **Thyroid cancer other than MTC26:** - 52% CCDC6 - 33% NCOA4 - 15% Other¶ §Unknown includes positive by FISH or PCR. ǁOthers included KIAA1468(2), ARHGAP12, CCDC88C, CLIP1, DOCK1+RBPMS, ERC1, PRKAR1A, and TRIM24 (all 1 each).25 ¶Others included CCDC1686, ERC1, KTN1, and RUFY (all 1 each).26 **NGS testing** - NGS allows for multiplex testing on a small amount of tissue for the detection of rare, as well as common, cancer-related biomarkers4,7,27 - _RET_ point mutations can be detected by NGS4-6 * * * Most common _RET_ mutations identified in the [LIBRETTO-001 phase I/II clinical trial](https://retevmo.lilly.com/hcp/efficacy/libretto-001?section=trial-design) 26: - 57% M918T - 19% Extracellular cysteine mutations - 16% Other# - 8% V804M/L #Others included D631-L633delinsE(5), E632-L633del(4), A883F(4), D631-L633delinsV(2), L790F(2), D898-E901del(2), D898\_E901del + D903\_S904delinsEP, K666N, T636-V637insCRT, D378-G385delinsE (all 1 each).26 ![The role of liquid biopsy in molecular profiling and clinical decision making](https://retevmo.lilly.com/assets/img/liquid-biopsy.svg) - While not recommended as a replacement for a diagnostic tissue biopsy, consider liquid biopsy when FFPE tumor tissue is unavailable or insufficient for molecular profiling11 - While a positive liquid biopsy result is considered reliable, a negative result requires confirmation with tumor tissue testing11 - NCCN Guidelines: principles of molecular and biomarker analysis in metastatic NSCLC2 - Plasma ctDNA (liquid biopsy) should not be used in lieu of a histologic tissue diagnosis - Studies have demonstrated liquid biopsy to generally have very high specificity but significantly compromised sensitivity, with a false-negative rate of up to 30% - Standards and guidelines for liquid biopsy testing for genetic alterations have not been established **Test for _RET_ 1** **Ensure your test can detect driver _RET_ fusions in NSCLC and non-medullary thyroid cancer and driver _RET_ mutations in MTC** ALK=anaplastic lymphoma kinase; BRAF=v-raf murine sarcoma viral oncogene homolog B; DNA=deoxyribonucleic acid; EGFR=epidermal growth factor receptor; FFPE=formalin-fixed paraffin-embedded; HER2=human epidermal growth factor receptor 2; KRAS=Kirsten rat sarcoma; MEK1=dual specificity mitogen-activated protein kinase kinase 1; METex14=mesenchymal-epithelial transition exon 14 skipping; MTC=medullary thyroid cancer; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer; NTRK=neurotrophic receptor tyrosine kinase; PIK3CA=phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; PTC=papillary thyroid cancer; _RET_ =rearranged during transfection; RNA=ribonucleic acid; ROS1=reactive oxygen species 1. [Savings & support](https://retevmo.lilly.com/hcp/savings-support) **References: 1.** Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. **2.** Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V5.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed December 1, 2022. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. **3.** Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V3.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed December 1, 2022. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. **4.** Gregg JP, Li T, Yoneda KY. Molecular testing strategies in non-small cell lung cancer: optimizing the diagnostic journey. _Transl Lung Cancer Res._ 2019;8(3):286-301. **5.** Suh JH, Schrock AB, Johnson A, et al. Hybrid capture-based comprehensive genomic profiling identifies lung cancer patients with well-characterized sensitizing epidermal growth factor receptor point mutations that were not detected by standard of care testing. _Oncologist._ 2018;23(7):776-781. **6.** Mertens F, Johansson B, Fioretos T, et al. The emerging complexity of gene fusions in cancer. _Nat Rev Cancer._ 2015;15(6):371-381. **7.** Suh JH, Johnson A, Albacker L, et al. Comprehensive genomic profiling facilitates implementation of the National Comprehensive Cancer Network Guidelines for lung cancer biomarker testing and identifies patients who may benefit from enrollment in mechanism-driven clinical trials. _Oncologist._ 2016;21(6):684-691. **8.** Drilon A, Hu ZI, Lai GGY, et al. Targeting _RET_-driven cancers: lessons from evolving preclinical and clinical landscapes. _Nat Rev Clin Oncol._ 2018;15(3):151-167. **9.** Ferrara R, Auger N, Auclin E, et al. Clinical and translational implications of _RET_ rearrangements in non-small cell lung cancer. _J Thorac Oncol._ 2018;13(1):27-45. **10.** Naidoo J, Drilon A. Molecular diagnostic testing in non-small cell lung cancer. _Am J Hematol Oncol._ 2014;10(4):4-11. **11.** Rolfo C, Mack PC, Scagliotti GV, et al. Liquid biopsy for advanced non-small cell lung cancer (NSCLC): a statement paper from the IASLC. _J Thorac Oncol._ 2018;13(9):1248-1268. **12.** Dietel M, Bubendorf L, Dingemans A-M, et al. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group. _Thorax._ 2016;71(2):177-184. **13.** Lindeman NI, Cagle PT, Aisner DL, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. _J Thorac Oncol._ 2018;13(3):323-358. **14.** Singal G, Miller PG, Agarwala V, et al. Association of patient characteristics and tumor genomics with clinical outcomes among patients with non-small cell lung cancer using a clinicogenomic database. _JAMA._ 2019;321:1391-1399. **15.** Fernandes MGO, Jacob M, Martins N, et al. Targeted gene next-generation sequencing panel in patients with advanced lung adenocarcinoma: paving the way for clinical implementation. _Cancers (Basel)._ 2019;11(9):1229. **16.** Hirsch FR, Scagliotti GV, Mulshine JL, et al. Lung cancer: current therapies and new targeted treatments. _Lancet._ 2017;389:299-311. **17.** Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in _RET_ fusion–positive non–small-cell lung cancer. _N Engl J Med._ 2020;383(9):813-824. **18.** Amatu A, Sartore-Bianchi A, Siena S. _NTRK_ gene fusions as novel targets of cancer therapy across multiple tumour types. _ESMO Open._ 2016;1(2):e000023. doi:10.1136/esmoopen-2015-000023. **19.** Vansteenkiste JF, Van De Kerkhove C, Wauters E, et al. Capmatinib for the treatment of non-small cell lung cancer. _Expert Rev Anticancer Ther._ 2019;19(8):659-671. **20.** FDA approves first targeted therapy to treat aggressive form of lung cancer. News release. FDA. May 6, 2020. Accessed May 21, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer. **21.** Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated _BRAF_(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. _Lancet Oncol._ 2016;17(7):984-993. **22.** FDA approves first targeted therapy for lung cancer mutation previously considered resistant to drug therapy. News release. FDA. May 28, 2021. Accessed June 17, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-lung-cancer-mutation-previously-considered-resistant-drug. **23.** FDA approves first targeted therapy for subset of non-small cell lung cancer. News release. FDA. May 21, 2021. Accessed June 30, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-subset-non-small-cell-lung-cancer. **24.** Chevallier M, Borgeaud M, Addeo A, Friedlaender A. Oncogenic driver mutations in non-small cell lung cancer: past, present and future. _World J Clin Oncol._ 2021;12(4):217-237. **25.** Zhao Z, Yang, X. Targeting HER2 alterations in non–small-cell lung cancer: a comprehensive review. _JCO Precis Oncol._ 2020;4:411-425. doi:10.1200/PO.19.00333. **26.** Benayed R, Offin M, Mullaney K, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. _Clin Cancer Res._ 2019;25(15):4712-4722. **27.** Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. _Thyroid._ 2015;25(6):567-610. **28.** Agrawal N, Jiao Y, Sausen M, et al. Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in _RET_ and _RAS_. _J Clin Endocrinol Metab._ 2013;98(2):E364-E369. **29.** Simbolo M, Mian C, Barollo S, et al. High-throughput mutation profiling improves diagnostic stratification of sporadic medullary thyroid carcinomas. _Virchows Arch._ 2014;465(1):73-78. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Retevmo Efficacy Overview [Skip to main content](https://retevmo.lilly.com/hcp/efficacy/libretto-001#maincontent) # Retevmo was evaluated in a phase I/II trial: the largest trial ever reported in patients with _RET_-driven cancer1-2 796 patients with _RET_-altered advanced or metastatic solid tumors were included in LIBRETTO-001, an open-label, single-arm, multicenter, phase I/II, multicohort trial.1-5\* ![Libretto-001 trial design chart with major efficacy outcomes and other efficacy outcomes](https://retevmo.lilly.com/assets/img/c-se-us-0280-se-hcp-all-eff-trial-design-image_trail-design-main_desktop.jpg) Up View Description LIBRETTO-001 included 796 patients, and the major efficacy outcomes were ORR and DoR; other efficacy outcomes included CNS ORR, CNS DoR, PFS, OS, time to response, and best change in tumor size from baseline.1,3,5 The overall safety analysis included 24 patients with other cancers, including cancers without a _RET_ alteration.4 **Phase 1 dose escalation:** Retevmo dosed at 20 mg QD–240 mg BID. Intra-patient dose escalation was allowed by protocol.3 **Phase 2 dose:** Retevmo dosed at 160 mg BID.3 **See full Prescribing Information for dosing instructions.** Objective response rate (ORR) was defined as complete response (CR) + partial response (PR) and was assessed by independent review committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.1 **The intent-to-treat (ITT) population was analyzed in the LIBRETTO-001 trial because this type of analysis avoids the selective exclusion of patients, which can lead to a biased assessment of an intervention's effectiveness.6-9** aPatients with advanced or metastatic _RET_ fusion-positive NSCLC who had progressed on platinum-based chemotherapy and those without prior systemic therapy were enrolled in separate cohorts.1 bEfficacy was evaluated in 41 patients, including those with the following tumor types: pancreatic adenocarcinoma (n=11); colorectal (n=10); salivary (n=4); unknown primary (n=3); breast (n=2); sarcoma (soft tissue) (n=2); xanthogranuloma (n=2); carcinoid (bronchial) (n=1); carcinoma of the skin (n=1); cholangiocarcinoma (n=1); ovarian (n=1); pulmonary carcinosarcoma (n=1); rectal neuroendocrine (n=1); small intestine (n=1).1 cEfficacy was evaluated in 247 adult patients with advanced or metastatic _RET_ fusion-positive NSCLC who were previously treated with platinum chemotherapy enrolled into a cohort of LIBRETTO-001. All 247 patients received systemic therapy (with a median of 2 prior systemic regimens). 144 of the 247 patients received prior anti-PD-1/PD-L1 therapy, and 85 of the 247 patients received a prior MKI.3 dNon-MTC by histology included papillary (n=54), poorly differentiated (n=6), anaplastic (n=4), and Hurthle cell (n=1).1 eNumber of patients included in the initial efficacy analysis. Efficacy was based on patients who had at least 6 months of follow-up.4 fPatients in this cohort received no prior systemic therapy other than RAI.1 gPatients in this cohort received a prior systemic therapy other than RAI.1 hThe efficacy of Retevmo was evaluated in 55 patients with RET-mutant advanced MTC who were previously treated with cabozantinib or vandetanib enrolled into a cohort of LIBRETTO-001.1 iPatients in this cohort could have received prior systemic therapies with a median of 2 prior systemic therapies (range 0-9).1 \*Pooled safety analysis: data as of June 15, 2021 BID=twice daily; CNS=central nervous system; CRC=colorectal cancer; DoR=duration of response; MKI=multikinase inhibitor; MTC=medullary thyroid cancer; NSCLC=non-small cell lung cancer; OS=overall survival; PD-1=programmed cell death 1; PD-L1=programmed death-ligand 1; PFS=progression-free survival; QD=once daily; _RET_ =rearranged during transfection. ## Retevmo demonstrated a consistent response in patients with certain _RET_-driven cancers in the LIBRETTO-001 trial1 ![Table showing the ORR and median DoR of Retevmo trial](https://retevmo.lilly.com/assets/img/c-se-us-0289-retevmo-trial-response-desktop.png) Up View Description **In patients with locally advanced or metastatic _RET_ fusion-positive NSCLC:** treatment-naive patients (n=69): 84% ORR (95% CI: 73, 92), median DoR was 20.2 months (95% CI: 13, NE); patients previously treated with platinum chemotherapy (n=247): 61% ORR (95% CI: 55, 67), median DoR was 28.6 months (95% CI: 20, NE). **In patients with advanced or metastatic _RET_ fusion-positive thyroid cancer (non-MTC):** systemic therapy-naive patients (n=24): 96% ORR (95% CI: 79, 100), median DoR not yet reached (95% CI: 42.8, NE); previously treated patients (n=41): 85% ORR (95% CI: 71, 94), median DoR was 26.7 months (95% CI: 12.1, NE). **In patients with advanced or metastatic _RET_ mutant-MTC:** cabozantinib/vandetanib treatment-naive patients (n=88): 81% ORR (95% CI: 71, 88), median DoR was not yet reached (95% CI: 51.3, NE); patients previously treated with cabozantinib and/or vandetanib (n=55): 76% ORR (95% CI: 63, 87), median DoR was 45.3 months (95% CI: 29.9, NE). Each paragraph is referenced to: Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. aEfficacy was evaluated in 247 adult patients with locally advanced or metastatic _RET_ fusion-positive NSCLC who were previously treated with platinum chemotherapy enrolled into a cohort of LIBRETTO-001. All 247 patients received systemic therapy (with a median of 2 prior systemic regimens).1 b Primary tumor histologies included papillary thyroid cancer, poorly differentiated thyroid cancer, anaplastic thyroid cancer, and Hurthle cell thyroid cancer.1 c Patients received no prior systemic therapy other than RAI.1 d Patients received a prior systemic therapy other than RAI.1 e The efficacy of Retevmo was evaluated in 55 patients with _RET_-mutant advanced MTC who were previously treated with cabozantinib or vandetanib enrolled into a cohort of LIBRETTO-001.1 The major efficacy outcome measures in LIBRETTO-001 were ORR and DoR. ORR was defined as CR + PR and was assessed by IRC according to RECIST v1.1.1 CI=confidence interval; CR=complete response; IRC=independent review committee; NE=not estimable; ORR=objective response rate; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors ## Retevmo had CNS activity in patients with locally advanced or metastatic _RET_ fusion-positive NSCLC and measurable brain metastases (n=21)1 CNS ORR was observed in the LIBRETTO-001 trial1 Of the 21 patients with measurable disease, 3 patients received RT to the brain within 2 months prior to study entry.1 ![patient CNS response in LIBRETTO-001 trial: baseline vs. Week 8 brain scan showing tumor reduction](https://retevmo.lilly.com/assets/img/c-se-us-0006-desktop.png) Up View Description Baseline and Week 8 scans from a patient in the LIBRETTO-001 trial who achieved a partial CNS response with Retevmo. Responses in intracranial lesions were observed in 4 of 5 treatment-naive patients. 38% of responders had a CNS DoR of ≥12 months. Responses in intracranial lesions were observed in 14 of 16 previously treated patients. 39% of responders had a CNS DoR of ≥12 months. Responses in intracranial lesions were observed in 86% of patients with measurable brain metastases (18/21). CNS ORR and CNS DoR were prespecified secondary endpoints that were evaluated and confirmed by an IRC.1,13 **Select Important Safety Information** **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. ## Retevmo was studied in 14 additional advanced or metastatic _RET_ fusion-positive solid tumors1 ![tumor agnostic cohort summary](https://retevmo.lilly.com/assets/img/tumor-agnostic-data-summary.jpg) Up View Description Tumor Agnostic Cohort (n=41) - ORR was 44% (95% CI: 28, 60); 4.9% CR + 39% PR - Median DoR was 24.5 months (95% CI: 9.2, NE) - The median follow-up was 14.9 months RET fusion positive pancreatic adenocarcinoma (n=11): - ORR was 55% (95% CI: 23, 83); 0% CR + 55% PR - DoR range was 2.5 months, 38.3+ months, based on 6 responders - Median prior systemic therapies: 2 RET fusion-positive CRC (n=10): - ORR was 20% (95% CI: 2.5, 56); 0% CR + 20% PR - DoR range was 5.6 months, 13.3 months based on 2 responders - Median prior systemic therapies: 3.5 aEfficacy was evaluated in 41 adult patients with locally advanced or metastatic _RET_ fusion-positive solid tumors. Thirty-seven patients received systemic therapy (with a median of 2 prior systemic regimens).1 The major efficacy outcome measures in LIBRETTO-001 were ORR and DoR. At the time of analysis (September 24, 2021), 50% of responses (n=9/18) were ongoing.5 All results reviewed by an IRC.1,7 Due to rounding, numbers presented may not add up to the totals indicated and percentages may not reflect the absolute figures for the same reason. **Because Retevmo is approved across all lines of therapy, including first line in certain _RET_-driven cancers, consider waiting for genomic test results, including _RET_ alteration results, before making therapeutic decisions1** **Select Important Safety Information** Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. ![Selpercatinib (Retevmo) is NCCN preferred](https://retevmo.lilly.com/assets/img/hcp-kcd-nccn_prefer-lung.svg) Selpercatinib (Retevmo) is a National Comprehensive Cancer Network® (NCCN®)-preferred (NCCN Category 2A††) treatment option for first-line or subsequent‡‡ therapy in patients with _RET_-positive metastatic non-small cell lung cancer (NSCLC)19§§ NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. **NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendations for NSCLC19:** Specific targeted therapies are the preferred systemic treatment options for eligible patients with metastatic NSCLC with certain driver alterations.‖‖ For patients with metastatic NSCLC who are _RET_ rearrangement positive, NCCN NSCLC Panel recommends selpercatinib (Retevmo) as a first-line or subsequent‡‡ therapy option (category 2A††) (preferred) for patients with metastatic NSCLC who are positive for _RET_ rearrangements. **NCCN Guidelines® recommendations for _RET_ alteration-positive differentiated thyroid cancers20:** Selpercatinib is a recommended systemic therapy option (category 2A††) in _RET_ fusion-positive: - Structurally persistent/recurrent locoregional or distant metastatic (including bone or CNS metastases) papillary carcinoma, follicular carcinoma, or oncocytic carcinoma, that is not amenable to RAI therapy Selpercatinib is a preferred systemic therapy option (category 2A††) in _RET_ fusion-positive: - Metastatic anaplastic carcinoma¶¶ Selpercatinib is a preferred systemic therapy option (category 1††) in _RET_ mutation-positive medullary carcinoma##: - Locoregional, unresectable carcinoma that is symptomatic or progressing by RECIST criteria - Distant metastatic, asymptomatic carcinoma that is unresectable and progressing by RECIST criteria - Distant metastatic, symptomatic or progressive carcinoma ††Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. ‡‡If _RET_ inhibitors have not been previously used. §§See the NCCN Guidelines for NSCLC for detailed recommendations, including other preferred treatment options. ‖‖The NCCN Guidelines for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories. ¶¶Molecular testing should include _BRAF_, _NTRK_, _ALK_, _RET_, MSI, dMMR, and tumor mutational burden. ## _RET_ somatic genotyping in patients who are germline wild-type or germline unknown. [See NCCN Guidelines for recommendations for _RET_ testing](https://retevmo.lilly.com/hcp/testing?section=nccn-guidelines) [See safety results for Retevmo](https://retevmo.lilly.com/hcp/safety) ALK=anaplastic lymphoma kinase; BRAF=v-raf murine sarcoma viral oncogene homolog B; CI=confidence interval; dMMR=DNA mismatch repair; MSI=microsatellite instability; NE=not estimable; NTRK=neurotrophic receptor tyrosine kinase. **References:** **1.** Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. **2.** Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). https://clinicaltrials.gov/ct2/show/NCT03157128. Updated June 9, 2022. Accessed June 14, 2022. **3.** Drilon A, Subbiah V, Gautschi O, et al. Durability of efficacy and safety with selpercatinib in patients with _RET_ fusion+ non-small-cell lung cancer: LIBRETTO-001. Poster presented at: European Lung Cancer Congress; March 30–April 2, 2022. Poster 27P. **4.** Data on File, Lilly USA, LLC, DOF-SE-US-0063. **5.** Subbiah V, Wolf J, Konda B, et al. Tumor agnostic efficacy of selpercatinib in patients with RET fusion-positive solid tumors: a global, multicenter trial updated (LIBRETTO-001). Presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago. Abstract 3094. **6.** Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in _RET_ fusion–positive non–small-cell lung cancer. _N Engl J Med._ 2020;383(9):813-824. **7.** Wirth LJ, Sherman E, Robinson B, et al. Efficacy of selpercatinib in _RET_-altered thyroid cancers. _N Engl J Med._ 2020;383(9):825-835. **8.** McCoy CE. Understanding the intention-to-treat principle in randomized controlled trials. _West J Emerg Med._ 2017;18(6):1075-1078. **9.** Gupta SK. Intention-to-treat concept: a review. _Perspect Clin Res._ 2011;2(3):109-112. **10.** Data on File, Lilly USA, LLC, DOF-SE-US-0058. **11.** Data on File, Lilly USA, LLC, DOF-SE-US-0028. **12.** Data on File, Lilly USA, LLC, DOF-SE-US-0013. **13.** Data on File, Lilly USA, LLC, DOF-SE-US-0033. **14.** Data on File, Lilly USA, LLC, DOF-SE-US-0031. **15.** Data on File, Lilly USA, LLC, DOF-SE-US-0032. **16.** Data on File, Lilly USA, LLC, DOF-SE-US-0024. **17.** Data on File, Lilly USA, LLC, DOF-SE-US-0069. **18.** Data on File, Lilly USA, LLC, DOF-SE-US-0067. **19.** Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V11.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed October 15, 2024. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. **20.** Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed Sept 23, 2024. To view the most recent and complete version of the guidelines, go online to https://www.nccn.org. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Retevmo Efficacy Trial [Skip to main content](https://retevmo.lilly.com/hcp/efficacy/libretto-431#maincontent) # LIBRETTO-431 **LIBRETTO-431: A Phase III superiority trial of Retevmo versus chemotherapy with or without pembrolizumab for patients with _RET_ fusion-positive advanced or metastatic NSCLC1-3** ![Image of trial design for LIBRETTO-431](https://retevmo.lilly.com/assets/img/c-se-us-0305_trialdesign-01.png) Up View description Chart showing trial design for LIBRETTO-431, a randomized, global, multicenter, open-label, Phase III trial that evaluated Retevmo versus chemotherapy (pemetrexed and carboplatin or cisplatin) with or without pembrolizumab in treatment-naive adult patients with _RET_ fusion-positive advanced or metastatic non-squamous NSCLC. Of the 261 total patients enrolled, 159 patients were randomized to Retevmo and 102 patients were randomized to chemotherapy with or without pembrolizumab. Crossover to Retevmo was optional for patients in the control arm upon confirmed progression as evaluated by IRC. (Footnote: The crossover rate to Retevmo on study was 61.8% (n=42/68). Off-study crossover to a selective _RET_ inhibitor occurred in an additional 15% of patients.) The primary efficacy endpoint was PFS for Retevmo, evaluated in ITT-pembro and in ITT populations; secondary endpoints included ORR, DoR, OS, CNS ORR, and CNS DoR. (Footnote: All primary and secondary endpoints listed were assessed by IRC per RECIST v1.1. CNS ORR and CNS DoR were also assessed per RANO-BM.) aPatients with brain metastases were eligible to be enrolled if asymptomatic and neurologically stable for 2 weeks. bThe crossover rate to Retevmo on study was 61.8% (n=42/68). Off-study crossover to a selective _RET_ inhibitor occurred in an additional 15% of patients. cAll primary and secondary endpoints listed were assessed by IRC per RECIST v1.1. CNS ORR and CNS DoR were also assessed per RANO-BM. Efficacy presentation focuses on the cohort of patients that investigators intended to treat with pembrolizumab (ITT-pembro), which included 129 patients who were randomized to Retevmo and 83 patients who were randomized to pembrolizumab plus chemotherapy. Retevmo was dosed at 160 mg BID. Pembrolizumab was dosed at 200 mg Q3W. Chemotherapy included pemetrexed (500 mg/m2 Q3W) and carboplatin (AUC 5 Q3W) or cisplatin (75 mg/m2 Q3W). Patients were stratified per investigator's choice of treatment with or without pembrolizumab if randomized to the control arm. Choice was declared prior to randomization. The subset of patients randomized with the intent not to receive pembrolizumab was less than 20% of total randomized patients, and is analyzed only as part of the intent-to-treat population. Additional stratification factors: geography, brain metastases at baseline per investigator assessment. AUC=area under the curve; BID=twice a day; CNS=central nervous system; DoR=duration of response; IRC=independent review committee; ITT=intent to treat; NSCLC=non-small cell lung cancer; ORR=overall response rate; PFS=progression-free survival; PD=progressive disease; Q3W=every three weeks; RANO-BM=Response Assessment in Neuro-Oncology Brain Metastases; RECIST=Response Evaluation Criteria in Solid Tumours; _RET_ =rearranged during transfection; SOC=standard of care ## PFS **In patients with advanced or metastatic _RET_ fusion-positive NSCLC** **Retevmo demonstrated superior PFS compared to pembrolizumab plus chemotherapy1,3** ![Kaplan-Meier curve showing progression-free survival](https://retevmo.lilly.com/assets/img/c-se-us_0302_pfs_desktop.png) Up View description This image shows median progression-free survival (PFS) in Retevmo-treated patients versus those treated with pembrolizumab plus chemotherapy. PFS was assessed in all randomized patients and was based on an interim analysis with a data cutoff date of May 1, 2023. For patients treated with Retevmo (n=129), median PFS was 24.8 months (95% CI: 16.9, NE) with median follow-up of 19.4 months. In patients treated with pembrolizumab plus chemotherapy (n=83), median PFS was 11.2 months (95% CI: 8.8, 16.8), with median follow-up of 18.9 months. An accompanying Kaplan-Meier curve shows progression-free survival for Retevmo-treated patients of 71.2% at 12 months and 58.6% at 18 months. PFS for patients treated with pembrolizumab plus chemotherapy was 47.8% at 12 months and 34.0% at 18 months. Hazard ratio was 0.47 (p=0.0002). PFS was assessed in all randomized patients. Based on an interim analysis with a data cutoff date of May 1, 2023.1,3 HR=hazard ratio; mPFS=median progression-free survival **Select Important Safety Information** **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. ## ORR and DoR **Objective response rate and duration of response for Retevmo vs pembrolizumab plus chemotherapy1,3** ![Image of ORR](https://retevmo.lilly.com/assets/img/c-se-us-0301_desktop.png) Up View description Graphic showing Objective Response Rate of 84% (95% CI: 76, 90) for Retevmo (n=129) versus 65% (95% CI: 54, 75) for pembrolizumab plus chemotherapy (n=83).7,9 Partial response (PR) for Retevmo was 77%; Complete Response (CR) for Retevmo was 7%. PR for pembrolizumab plus chemotherapy was 59%; CR for pembrolizumab plus chemotherapy was 6%. ![Image of median DoR](https://retevmo.lilly.com/assets/img/c-se-us-0301_2_desktop.png) Up View description Graphic showing median Duration of Response of 24.2 months (95% CI: 17.9, NE) for Retevmo (n=129) versus 11.5 months (95% CI: 9.7, 23.3) with pembrolizumab plus chemotherapy (n=83)7,9 ORR, a secondary endpoint, was defined as CR+PR and was assessed by the IRC according to RECIST v1.1.1 Based on an interim analysis with a data cutoff date of May 1, 2023.1,2 Overall survival (OS) is immature. At a May 2024 interim analysis of OS, a total of 31% and 25% of patients died in the Retevmo and the control arm, respectively, with an OS HR of 1.26 (95% CI: 0.78, 2.04). Overall survival results may be affected by the imbalance in post-progression therapies. At disease progression, nearly three-quarters (50 of 68 patients) in the control arm received Retevmo, while fewer than one-quarter (16 of 71 patients) in the Retevmo arm received chemotherapy, immune check point inhibitor, or both. CI=confidence interval; CR=complete response; DoR=duration of response; NE=not estimable; PR=partial response ## 431 CNS ORR and DoR **Retevmo had CNS activity¶ in patients with _RET_ fusion-positive advanced or metastatic NSCLC1,3** **Responses in patients with measurable CNS metastases at baseline** ![Libretto 431 CNS ORR 82% Retevmo, 58% pembrolizumab + chemotherapy](https://retevmo.lilly.com/assets/img/c-se-us-0306_cns-orr-dor-1-2800px-ux.png) Up View description Image showing central nervous system Objective Response Rate for Retevmo versus pembrolizumab plus chemotherapy. CNS ORR for Retevmo (n=17) was 82% (95% CI: 57, 96). Within this group, 47% of patients showed partial response and 35% showed complete response. In patients treated with pembrolizumab plus chemotherapy (n=12), CNS ORR was 58% (95% CI: 28, 85). Within this group, 42% of patients showed partial response and 17% showed complete response. ![Libretto 431 CNS median DoR, Not Yet Reached Retevmo, 13.4 months pembrolizumab + chemotherapy](https://retevmo.lilly.com/assets/img/c-se-us-0306_cns-orr-dor-2-2800px-ux.png) Up View description Image showing central nervous system median duration of response for Retevmo versus pembrolizumab plus chemotherapy. CNS median DoR for Retevmo (n=14) was not yet reached (95% CI: 7.6, NE). Median follow-up for this group was 9.9 months. In patients treated with pembrolizumab plus chemotherapy (n=7), CNS median DoR was 13.4 months (95% CI: 3.5, NE). Median follow-up for this group was 12.7 months. CNS ORR (defined as CR+PR) and CNS DoR were prespecified secondary endpoints in the LIBRETTO-431 trial and were evaluated and assessed by IRC according to RECIST v1.1.1,3 Based on an interim analysis with a data cutoff date of May 1, 2023.1,3 ITT=intent to treat Due to rounding, percentages presented may not add up to the indicated totals. ¶CNS activity is defined as shrinking current lesions and preventing the occurrence of new CNS lesions. **Select Important Safety Information** Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. ## 431 Risk of CNS Progression **Risk of CNS as the first site of progression was reduced with Retevmo compared to pembrolizumab plus chemotherapy1,3** **12-Month CIR for Patients with or without Baseline CNS Metastases (N=192)** ![Libretto 431 5.5% Retevmo, 20.3% pembrolizumab + chemotherapy](https://retevmo.lilly.com/assets/img/c-se-us-0307_visreps_desktop.png) Up View description The 12-month CIR for patients with and without baseline CNS metastases was 5.5% with Retevmo compared to 20.3% with pembrolizumab plus chemotherapy. The 95% confidence intervals were 2.2% to 10.8% and 11.3% to 31.1%, respectively. The cause-specific hazard ratio was 0.28 with a 95% confidence interval of 0.12 to 0.68. Cause-specific HR for CNS progression accounts for competing risks of non-CNS PD and death. a Cause-specific HR for CNS progression accounts for competing risks of non-CNS PD and death. ![Libretto 431 patients with CNS matastases at baseline and patients without cns metastases at baseline comparison chart](https://retevmo.lilly.com/assets/img/0307-2-750-ux.png) Up View description The 12-month CIR for patients with baseline CNS metastases was 25.7% with Retevmo compared to 33.3% with pembrolizumab plus chemotherapy. The 95% confidence intervals were 8.8% to 46.7% and 14.3% to 53.8%, respectively. The cause-specific hazard ratio was 0.61 with a 95% confidence interval of 0.19 to 1.92. The 12-month CIR for patients without baseline CNS metastases was 1.1% with Retevmo compared to 14.7% with pembrolizumab plus chemotherapy. The 95% confidence intervals were 0.1% to 5.2% and 5.7% to 27.6%, respectively. The cause-specific hazard ratio was 0.17 with a 95% confidence interval of 0.04 to 0.69. Cause-specific HR for CNS progression accounts for competing risks of non-CNS PD and death. a Cause-specific HR for CNS progression accounts for competing risks of non-CNS PD and death. Intracranial evaluation with CT or MRI was required for all patients at baseline and subsequently at the same frequency as other radiologic imaging and as clinically indicated. All results reviewed by IRC.1,3 CIR=cumulative incidence rate; CT=computerized tomography ## Safety **Safety and tolerability were evaluated in LIBRETTO-4311** Adverse Events (≥15%) in Patients Who Received Retevmo in LIBRETTO-4311 ![Table of adverse events in patients who received Retevmo in LIBRETTO-431](https://retevmo.lilly.com/assets/img/c-se-us-0303_ar.png) Up View description Adverse Event table - **Retevmo, Adverse Reactions Grades 1-4:** In Retevmo-treated patients (n=158), patients experienced Grades 1-4 Vascular Disorders including hypertension (48%). Patients experienced Grade 1-4 Gastrointestinal Disorders including diarrhea (44%), dry mouth (39%), abdominal pain (25%), constipation (22%), stomatitis (18%), nausea (13%), and vomiting (13%). Grades 1-4 General disorders and administrative site conditions included edema (41%), fatigue (32%), and pyrexia (13%). Grades 1-4 Skin and subcutaneous tissue disorders included rash (33%). Grades 1-4 Musculoskeletal and connective tissue disorders included musculoskeletal pain (25%). Grades 1-4 Investigations included Electrocardiogram QT prolonged (20%). Grades 1-4 Metabolism and nutrition disorders included decreased appetite (17%). Infections and infestations included COVID19 infection (19%). - **Retevmo, Adverse Reactions Grades 3-4:** In Retevmo-treated patients (n=158), Grade 3-4 Vascular Disorders included hypertension (20%). Grade 3-4 Gastrointestinal Disorders included diarrhea (1.3%), dry mouth (0%), abdominal pain (0.6%), constipation (0%), stomatitis (0%), nausea (0%), and vomiting (0%). Grade 3-4 General disorders and administrative site conditions included edema (2.5%), fatigue (3.2%), and pyrexia (0.6%). Grade 3-4 Skin and subcutaneous tissue disorders included rash (1.9%). Grade 3-4 Musculoskeletal and connective tissue disorders included musculoskeletal pain (0%). Grade 3-4 Investigations included Electrocardiogram QT prolonged (9.0%). Grade 3-4 Metabolism and nutrition disorders included decreased appetite (0%). Infections and infestations included COVID-19 infection (0.6%). - **Chemotherapy with or without pembrolizumab, Grades 1-4:** In patients treated with chemotherapy with or without pembrolizumab (n=98), Grades 1-4 Vascular Disorders included hypertension (7%). Patients experienced Grades 1-4 Gastrointestinal Disorders including diarrhea (24%), dry mouth (6%), abdominal pain (19%), constipation (40%), stomatitis (16%), nausea (44%), and vomiting (23%). Grades 1-4 General disorders and administrative site conditions included edema (28%), fatigue (50%), and pyrexia (23%). Grades 1-4 Skin and subcutaneous tissue disorders included rash (30%). Grades 1- 4 Musculoskeletal and connective tissue disorders included musculoskeletal pain (28%). Grades 1-4 Investigations included Electrocardiogram QT prolonged (1.0%). Grades 1-4 Metabolism and nutrition disorders included decreased appetite (34%). Infections and infestations included COVID-19 infection (18%). - **Chemotherapy with or without pembrolizumab, Grades 3-4:** For those undergoing chemotherapy with or without pembrolizumab (n=98), Grade 3-4 Vascular Disorders included hypertension (3.1%). Grade 3-4 Gastrointestinal Disorders included diarrhea (2.0%), dry mouth (0%), abdominal pain (2.0%), constipation (1.0%), stomatitis (0%), nausea (1.0%), and vomiting (1.0%). Grade 3-4 General disorders and administrative site conditions included edema (0%), fatigue (5.0%), and pyrexia (0%). Grade 3-4 Skin and subcutaneous tissue disorders included rash (1.0%). Grade 3-4 Musculoskeletal and connective tissue disorders included musculoskeletal pain (0%). Grade 3-4 Investigations included Electrocardiogram QT prolonged (0%). Grade 3-4 Metabolism and nutrition disorders included decreased appetite (2.0%). Infections and infestations included COVID-19 infection (0%). - Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. \*No Grade 4 abnormalities were reported. #Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Select Laboratory Abnormalities (≥20%) Worsening from Baseline in Patients Who Received Retevmo in LIBRETTO-4311 ![Table of laboratory abnormalities in patients who received Retevmo in LIBRETTO-431](https://retevmo.lilly.com/assets/img/c-se-us-0303_aes_lababs.png) Up View description Lab abnormality table - Retevmo, Laboratory Abnormalities Grades 1-4: In Retevmo-treated patients (n=158), Grades 1-4 Chemistry abnormalities included ALT increased (81%), AST increased (77%), alkaline phosphatase increased (35%), total bilirubin increased (52%), blood creatinine increased (23%), magnesium decreased (16%), albumin decreased (25%), calcium decreased (53%), sodium decreased (31%), and potassium decreased (17%). Grades 1-4 Hematology abnormalities included platelets decreased (53%), lymphocyte count decreased (53%), hemoglobin decreased (21%), and neutrophil count decreased (53%). - Retevmo, Laboratory Abnormalities Grades 3-4: In Retevmo-treated patients (n=158), Grades 3-4 Chemistry abnormalities included ALT increased (21%), AST increased (10%), alkaline phosphatase increased (1.3%), total bilirubin increased (1.3%), blood creatinine increased (0%), magnesium decreased (0.6%), albumin decreased (0%), calcium decreased (1.9%), sodium decreased (3.2%), and potassium decreased (1.3%). Grades 3-4 Hematology abnormalities included platelets decreased (3.2%), lymphocyte count decreased (8%), hemoglobin decreased (0%), and neutrophil count decreased (2.0%). - Chemotherapy with or without pembrolizumab, Laboratory Abnormalities Grades 1-4: In patients treated with chemotherapy with or without pembrolizumab (n=98), Grades 1-4 Chemistry abnormalities included ALT increased (63%), AST increased (46%), alkaline phosphatase increased (22%), total bilirubin increased (9%), blood creatinine increased (21%), magnesium decreased (8%), albumin decreased (5%), calcium decreased (24%), sodium decreased (41%), and potassium decreased (15%). Grades 1-4 Hematology abnormalities included platelets decreased (39%), lymphocyte count decreased (64%), hemoglobin decreased (91%), and neutrophil count decreased (58%). - Chemotherapy with or without pembrolizumab, Laboratory Abnormalities Grades 3-4: For those undergoing chemotherapy with or without pembrolizumab (n=98), Grades 3-4 Chemistry abnormalities included ALT increased (4.1%), AST increased (0%), alkaline phosphatase increased (0%), total bilirubin increased (0%), blood creatinine increased (0%), magnesium decreased (0%), albumin decreased (0%), calcium decreased (1.0%), sodium decreased (2.1%), and potassium decreased (1.0%). Grades 3-4 Hematology abnormalities included platelets decreased (5%), lymphocyte count decreased (15%), hemoglobin decreased (5%), and neutrophil count decreased (11%). - Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 a Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available: RETEVMO (range: 154 to 157 patients) and chemotherapy with or without pembrolizumab (range: 96 to 97 patients) #Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. - Based on an interim analysis with a data cutoff date of May 1, 2023.1,3 - Serious adverse reactions occurred in 35% of patients who received Retevmo. The most frequent serious adverse reactions (≥2% of patients) were pleural effusion, and abnormal hepatic function.1 - Fatal adverse reactions occurred in 4.4% of patients who received Retevmo; fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1, each).1 - Permanent discontinuation due to an adverse reaction occurred in 10% of patients who received Retevmo. Adverse reactions resulting in permanent discontinuation in ≥1% of patients included increased ALT (1.3%), and myocardial infarction (1.3%).1 - Dosage interruptions due to an adverse reaction occurred in 72% of patients who received Retevmo. Adverse reactions requiring dosage interruption in ≥5% of patients included increased ALT, hypertension, increased AST, QT prolongation, diarrhea, and COVID-19 infection.1 - Dose reductions due to an adverse reaction occurred in 51% of patients who received Retevmo. Adverse reactions requiring dose reductions in ≥5% of patients included increased ALT, increased AST, QT prolongation.1 - Clinically relevant adverse reactions in <15% of patients who received Retevmo include headache (14%); hemorrhage (13%); urinary tract infections (12%); hypothyroidism (9%); pneumonia (9%); dizziness (8%); interstitial lung disease/pneumonitis (4.4%); hypersensitivity, chylous ascites, and chylothorax (all < 2%).1 See full Prescribing Information for more information on adverse reactions, laboratory abnormalities, and dose modifications. AE=adverse event; ALT=alanine transaminase; AST=aspartate transferase; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute; WBC=white blood cell ## Summary **In the 1L treatment of advanced or metastatic _RET_-fusion positive NSCLC** **Retevmo is the first and only targeted agent to have demonstrated superior PFS in a Phase III head-to-head trial against pembrolizumab plus chemotherapy1** - LIBRETTO-431 (N=261) was a randomized, global, multicenter, open-label, Phase III trial that evaluated Retevmo versus chemotherapy with or without pembrolizumab in treatment-naive adult patients with advanced or metastatic _RET_ fusion-positive NSCLC, including those with brain metastases. - The primary endpoint was PFS for Retevmo versus chemotherapy with pembrolizumab. - 10% of patients permanently discontinued treatment due to AEs with Retevmo (n=16/158) **Retevmo may affect both healthy cells and tumor cells, which can result in side effects, some of which can be serious.1** Based on an interim analysis with a data cutoff date of May 1, 2023.1,4 ![Graphic of LIBRETTO-431 summary](https://retevmo.lilly.com/assets/img/c-se-us-0308.png) Up View description Median PFS for Retevmo (n=129) with oral administration was 24.8 months (95% CI: 16.9, NE). Median PFS for pembrolizumab plus chemotherapy (n=83) with IV administration was 11.2 months (95% CI: 8.8, 16.8). ORR for Retevmo was 84% (95% CI: 76, 90). ORR for pembrolizumab plus chemotherapy was 65% (95% CI: 54, 75). Median DoR for Retevmo was 24.2 months (95% CI: 17.9, NE). Median DoR for pembrolizumab plus chemotherapy was 11.5 months (95% CI: 9.7, 23.3). 1L=first line; INV=investigator NSCLC Summary **For patients with locally advanced or metastatic NSCLC** **Retevmo was granted approval based on LIBRETTO-001, a Phase I/II trial1,5** ## **LIBRETTO-001 Trial Design** The phase I/II, multicohort, open-label, single-arm, multicenter LIBRETTO-001 trial enrolled a pooled safety population of 796 patients, including patients with locally advanced or metastatic _RET_ fusion-positive NSCLC.\* Major efficacy outcomes were ORR and DoR. Other efficacy outcomes, evaluated in subsets of patients, included CNS ORR, CNS DoR, PFS, OS, time to response, and best change in tumor size from baseline. In phase II, the dose for Retevmo was 160 mg PO BID.1,5-7 The pooled safety population also included patients with advanced or metastatic _RET_ fusion-positive thyroid cancer (non-MTC),† patients with advanced or metastatic _RET_-mutant MTC, patients with _RET_ fusion-positive solid tumors (other than NSCLC or thyroid),‡ and patients with other cancers, including cancers without a _RET_ alteration.5 \*Patients with locally advanced or metastatic _RET_ fusion-positive NSCLC who had progressed on platinum-based chemotherapy and those without prior systemic therapy were enrolled in separate cohorts.1 †Non-MTC by histology included papillary (n=54), poorly differentiated (n=6), anaplastic (n=4), and Hurthle cell (n=1).1 ‡Other _RET_ fusion-positive solid tumors included pancreatic cancer (n=11), colon cancer (n=10), and salivary cancer (n=4).1 PO=orally ![Chart of efficacy outcomes](https://retevmo.lilly.com/assets/img/c-se-us-0300_desktop.png) Up View description Graphic showing Major Efficacy Outcomes and Secondary Endpoints for treatment-naive patients (n=69) and patients previously treated with platinum chemotherapy (n=247; image footnote: Efficacy was evaluated in 247 adult patients with locally advanced or metastatic _RET_ fusion-positive NSCLC who were previously treated with platinum chemotherapy enrolled into a cohort of LIBRETTO-001. All 247 patients received systemic therapy (with a median of 2 prior systemic regimens). Among treatment-naive patients (n=69), Objective Response Rate was 84% (95% confidence interval: 73, 92). Median Duration of Response (DoR) was 20.2 months (95% confidence interval: 13, NE). Median follow-up was 20.3 months. Among patients previously treated with platinum chemotherapy (n=247), Objective Response Rate was 61% (95% confidence interval: 55, 67). Median Duration of Response (DoR) was 28.6 months (95% confidence interval: 20, NE). Median follow-up was 21.2 months. Secondary endpoints were CNS ORR and CNS DoR. Of the 21 patients with measurable disease, 3 patients received radiation therapy to the brain within 2 months prior to study entry. Among treatment-naive patients (n=69), 4 of 5 patients had CNS ORR response. On CNS DoR, 38% had intracranial DoR of greater than 12 months. Among patients previously treated with platinum chemotherapy (n=247), 14 of 16 had CNS ORR response. On CNS DoR, 39% had intracranial DoR of greater than 12 months. - Time-to-event endpoints are not interpretable in a single-arm study. The clinical significance of this descriptive analysis is not known. - ORR was defined as CR + PR and was assessed by IRC according to RECIST v1.1.1 - ORR, DoR, CNS ORR, CNS DoR results reviewed by an IRC.1 - CNS ORR was a prespecified secondary endpoint that was evaluated and confirmed by an IRC.1 a Efficacy was evaluated in 247 adult patients with locally advanced or metastatic _RET_ fusion-positive NSCLC who were previously treated with platinum chemotherapy enrolled into a cohort of LIBRETTO-001. All 247 patients received systemic therapy (with a median of 2 prior systemic regimens).1 RT=radiation therapy Select Important Safety Information **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. **References:** **1.** Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. **2.** Solomon BJ, Zhou CC, Drilon A, et al. Phase III study of selpercatinib versus chemotherapy ± pembrolizumab in untreated RET positive non-small-cell lung cancer. _Future Oncol_. 2021;17(7):763-773. **3.** Zhou C, Solomon B, Loong HH, et al. First-line selpercatinib or chemotherapy and pembrolizumab in _RET_ fusion-positive NSCLC. _N Engl J Med_. 2023;389(20):1839-1850. doi:10.1056/NEJMoa2309457 **4.** Data on File. Lilly USA, LLC. DOF-SE-US-0077. **5.** Drilon A, Subbiah V, Gautschi O, et al. Selpercatinib in patients with RET fusion-positive non-small-cell lung cancer: updated safety and efficacy from the registrational LIBRETTO-001 phase I/II trial. _J Clin Oncol_. 2023;41(2):385-394. **6.** Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). https://clinicaltrials.gov/ct2/show/NCT03157128. Updated June 9, 2022. Accessed June 14, 2022. **7.** Data on File, Lilly USA, LLC, DOF-SE-US-0063. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Retevmo Efficacy in MTC [Skip to main content](https://retevmo.lilly.com/hcp/efficacy/libretto-531#maincontent) # LIBRETTO-531 ## LIBRETTO-531: A Phase III superiority trial evaluating Retevmo versus cabozantinib or vandetanib in _RET_-mutant advanced or metastatic MTC 1,2\*†‡ ![Image of trial design for LIBRETTO-531](https://retevmo.lilly.com/assets/img/c-se-us-0312_trial-design-01.png) Up View description Chart showing trial design for LIBRETTO-531. Patients with kinase inhibitor-naive _RET_-mutant MTC (N=291) were randomized 2:1. One hundred ninety-three patients were randomized to Retevmo; 98 patients were randomized to cabozantinib or vandetanib. (73 patients and 25 patients received cabozantinib and vandetanib, respectively, within the control arm. Stratification factors: investigator’s choice of treatment if randomized to control arm \[choice/intent of treatment regimen must be declared prior to randomization\], mutation status \[M918T versus other\].) Crossover to Retevmo was optional for patients in the control arm upon disease progression (PD) confirmed by IRC. The primary endpoint was PFS. Secondary endpoints included ORR, DoR and OS. (All primary and secondary endpoints listed were reviewed by IRC per RECIST v1.1.) a PD was confirmed by IRC - Trial excluded patients who had presence of other validated oncogenic drivers. - Retevmo was dosed at 160 mg BID. Cabozantinib was dosed at 140 mg QD and vandetanib was dosed at 300 mg QD. \*All primary and secondary endpoints listed were reviewed by IRC per RECIST v1.1. †Stratification factors: investigator’s choice of treatment if randomized to control arm (choice/intent of treatment regimen must be declared prior to randomization), mutation status (M918T versus other).1 ‡73 patients and 25 patients received cabozantinib and vandetanib, respectively, within the control arm. Numerical imbalance may be due to worldwide supply shortage of vandetanib during the trial.2 BID=twice a day; DoR=duration of response; IRC=independent review committee; MTC=medullary thyroid cancer; ORR=overall response rate; PD=progressive disease; PFS=progression-free survival; QD=every day; RECIST=Response Evaluation Criteria in Solid Tumours; _RET_ =rearranged during transfection ## PFS **In patients with _RET_-mutant advanced or metastatic MTC** **Retevmo demonstrated superior PFS compared to cabozantinib or vandetanib1,2** ![Kaplan-Meier curve showing progression-free survival for Retevmo-treated patients versus cabozantinb](https://retevmo.lilly.com/assets/img/c-se-us-0313_pfs-v2_desktop.png) Up View description This image shows median PFS in Retevmo-treated patients (n=193) versus those treated with cabozantinib or vandetanib (n=98). PFS was assessed in all randomized patients and was based on an interim analysis with a data cutoff date of May 22, 2023. For patients treated with Retevmo, median PFS was not yet reached (95% CI not estimable) with median follow-up of 12.5 months. In patients treated with cabozantinib or vandetanib, median PFS was 16.8 months (95% CI: 12.2, 25.1) with median follow-up of 11.0 months. An accompanying Kaplan-Meier curve shows progression-free survival for Retevmo-treated patients of 86% at 12 months. PFS for patients treated with cabozantinib or vandetanib was 66% at 12 months. Hazard ratio was 0.28 (p<0.0001). PFS was assessed in all randomized patients. Based on an interim analysis with a data cutoff date of May 22, 2023.1,2 HR=hazard ratio; NE=not estimable **Select Important Safety Information** **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. ## ORR and DoR **Overall response rate and duration of response for Retevmo vs cabozantinib or vandetanib1,2,§** ![Overall Response Rate for Retevmo versus cabozantinib or vandetanib](https://retevmo.lilly.com/assets/img/orr.png) Up View description Image showing Overall Response Rate for Retevmo versus cabozantinib or vandetanib. ORR for Retevmo (n=193) was 69% (95% CI: 62, 76). Within this group, 58% of patients showed Partial Response and 12% showed Complete Response. In patients treated with cabozantinib or vandetanib (n=98), ORR was 39% (95% CI: 29, 49). Within this group, 35% of patients showed Partial Response and 4% showed Complete Response. ![Median duration of response for Retevmo versus cabozantinib or vandetanib](https://retevmo.lilly.com/assets/img/median_dor.png) Up View description Image showing Duration of Response for Retevmo versus cabozantinib or vandetanib. DoR for Retevmo was not yet reached (95% CI: NE, NE). Median follow-up was 11.1 months. In patients treated with cabozantinib or vandetanib DoR was 16.6 months (95% CI: 10.4, NE). Median follow-up was 12.8 months. - ORR, a secondary endpoint, was defined as CR+PR and was assessed by the IRC according to RECIST v1.1. - Based on an interim analysis with a data cutoff date of May 22, 2023.1,2 - At the time of this analysis, overall survival (OS) data were immature with 18 deaths observed.1 §Due to rounding, percentages presented may not add up to the indicated totals. CI=confidence interval; CR=complete response; PR=partial response ## Safety **Safety and tolerability were evaluated for Retevmo in LIBRETTO-5311** Adverse Events (≥10%) in Patients Who Received Retevmo in LIBRETTO-531 ![Table of adverse events in patients who received Retevmo in LIBRETTO-531](https://retevmo.lilly.com/assets/img/c-se-us-0315_aes-and-lab-abs3-v2.png) Up View description Adverse Events (≥10%) in Patients Who Received Retevmo in LIBRETTO-531 **Retevmo, Grades 1-4:** In Retevmo-treated patients (n=193), Vascular disorders of Grades 1-4 included hypertension (43%). General disorders and administration-site conditions of Grades 1-4 included edema (33%), fatigue (28%), and pyrexia (12%). Gastrointestinal disorders of Grades 1-4 included dry mouth (32%), diarrhea (26%), abdominal pain (18%), constipation (16%), stomatitis (14%), pyrexia (12%), and nausea (10%). Nervous system disorders of Grades 1-4 included headache (23%). Skin and subcutaneous tissue disorders of Grades 1-4 included rash (19%). Reproductive system and breast disorders of Grades 1-4 included erectile dysfunction (16%). Investigations category included electrocardiogram QT prolonged (14%). Metabolism and nutrition disorders of Grades 1-4 included decreased appetite (12%). Endocrine disorders of Grades 1-4 included hypothyroidism (11%). **Retevmo, Grades 3-4:** In Retevmo-treated patients (n=193), Vascular disorders of Grades 3-4 included hypertension (19%). General disorders and administration-site conditions of Grades 3-4 included edema (0.0%), fatigue (4.1%), and pyrexia (1.0%). Gastrointestinal disorders of Grades 3-4 included dry mouth (0.5%), diarrhea (3.1%), abdominal pain (0.5%), constipation (0.0%), stomatitis (0.5%), pyrexia (1.0%), and nausea (1.0%). Nervous system disorders of Grades 3-4 included headache (0.5%). Skin and subcutaneous tissue disorders of Grades 3-4 included rash (1.6%). Reproductive system and breast disorders of Grades 3-4 included erectile dysfunction (0.0%). Investigations category included electrocardiogram QT prolonged (4.7%). Metabolism and nutrition disorders of Grades 3-4 included decreased appetite (0.5%). Endocrine disorders of Grades 3-4 included hypothyroidism (0.0%). All non-zero values for Retevmo Grades 3-4 are footnoted to indicate: “Only includes a Grade 3 adverse reaction.” **Cabozantinib or Vandetanib, Grades 1-4:** In cabozantinib- or vandetanib-treated patients (n=97), Vascular disorders of Grades 1-4 included hypertension (41%). General disorders and administration-site conditions of Grades 1-4 included edema (5%), fatigue (47%), and pyrexia (2.1%). Gastrointestinal disorders of Grades 1-4 included dry mouth (10%), diarrhea (61%), abdominal pain (21%), constipation (12%), stomatitis (42%), pyrexia (2.1%), and nausea (32%). Nervous system disorders of Grades 1-4 included headache (21%). Skin and subcutaneous tissue disorders of Grades 1-4 included rash (27%). Reproductive system and breast disorders of Grades 1-4 included erectile dysfunction (0.0%). Investigations category included electrocardiogram QT prolonged (13%). Metabolism and nutrition disorders of Grades 1-4 included decreased appetite (28%). Endocrine disorders of Grades 1-4 included hypothyroidism (21%). **Cabozantinib or Vandetanib, Grades 3-4:** In cabozantinib- or vandetanib-treated patients (n=97), Vascular disorders of Grades 3-4 included hypertension (18%). General disorders and administration-site conditions of Grades 3-4 included edema (0.0%), fatigue (9%), and pyrexia (0.0%). Gastrointestinal disorders of Grades 3-4 included dry mouth (1.0%), diarrhea (8%), abdominal pain (2.1%), constipation (0.0%), stomatitis (13%), pyrexia (0.0%), and nausea (5%). Nervous system disorders of Grades 3-4 included headache (0.0%). Skin and subcutaneous tissue disorders of Grades 3-4 included rash (4.1%). Reproductive system and breast disorders of Grades 3-4 included erectile dysfunction (0.0%). Investigations category included electrocardiogram QT prolonged (2.1%). Metabolism and nutrition disorders of Grades 3-4 included decreased appetite (5%). Endocrine disorders of Grades 3-4 included hypothyroidism (0.0%). All non-zero values for Cabozantinib or Vandetanib Grades 3-4 are footnoted to indicate: “Only includes a Grade 3 adverse reaction.” Footnote: Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. \*Only includes a Grade 3 adverse reaction #Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Select Laboratory Abnormalities (≥5%) Worsening from Baseline in Patients Treated with Retevmo in LIBRETTO-531 ![Table of laboratory abnormalities](https://retevmo.lilly.com/assets/img/c-se-us-0315_aes-and-lab-abs4.png) Up View description Select Laboratory Abnormalities (≥5%) Worsening from Baseline in Patients Treated with Retevmo in LIBRETTO-531 **Retevmo, Grades 1-4:** In Retevmo-treated patients, Chemistry-related laboratory abnormalities of Grades 1-4 included calcium decreased (55%), ALT increased (53%), AST increased (47%), alkaline phosphatase increased (37%), total bilirubin increased (32%), blood creatinine increased (27%) sodium decreased (20%), albumin decreased (11%), magnesium decreased (9%), and potassium decreased (8%). Hematology-related laboratory abnormalities of Grades 1-4 included lymphocyte count decreased (41%), neutrophil count decreased (33%), platelets decreased (28%), and hemoglobin decreased (18%). **Retevmo, Grades 3-4:** In Retevmo-treated patients, Chemistry-related laboratory abnormalities of Grades 3-4 included calcium decreased (5%), ALT increased (16%), AST increased (5%), alkaline phosphatase increased (6%), total bilirubin increased (1.1%), blood creatinine increased (6%) sodium decreased (3.2%; Grade 3 AE only), albumin decreased (1.1%), magnesium decreased (3.3%), and potassium decreased (0.0%). Hematology-related laboratory abnormalities of Grades 3-4 included lymphocyte count decreased (18%), neutrophil count decreased (14%), platelets decreased (1.1%), and hemoglobin decreased (2.1%; Grade 3 AE only). **Cabozantinib or Vandetanib, Grades 1-4:** In cabozantinib- or vandetanib-treated patients, Chemistry-related laboratory abnormalities of Grades 1-4 included calcium decreased (62%), ALT increased (72%), AST increased (68%), alkaline phosphatase increased (28%), total bilirubin increased (30%), blood creatinine increased (16%) sodium decreased (16%), albumin decreased (7%), magnesium decreased (26%), and potassium decreased (22%). Hematology-related laboratory abnormalities of Grades 1-4 included lymphocyte count decreased (36%), neutrophil count decreased (42%), platelets decreased (34%), and hemoglobin decreased (23%). **Cabozantinib or Vandetanib, Grades 3-4:** In cabozantinib- or vandetanib-treated patients, Chemistry-related laboratory abnormalities of Grades 3-4 included calcium decreased (11%), ALT increased (7%; Grade 3 AE only), AST increased (3.2%), alkaline phosphatase increased (5%), total bilirubin increased (3.2%; Grade 3 AE only), blood creatinine increased (8%) sodium decreased (0.0%), albumin decreased (0.0%), magnesium decreased (9%), and potassium decreased (4.4%; Grade 3 AE only). Hematology-related laboratory abnormalities of Grades 3-4 included lymphocyte count decreased (13%), neutrophil count decreased (19%), platelets decreased (1.1%; Grade 3 AE only), and hemoglobin decreased (2.1%; Grade 3 AE only). Treatment group footnote: Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available: Retevmo (range: 183 to 191 patients) and chemotherapy with or without cabozantinib or vandetanib (range: 91 to 94 patients). a Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available: Retevmo (range: 183 to 191 patients) and chemotherapy with or without cabozantinib or vandetanib (range: 91 to 94 patients).1 - Serious adverse reactions occurred in 22% of patients who received Retevmo. The most frequent serious adverse reactions were pneumonia and pyrexia (n = 3, each) and hypertension and urinary tract infection (n = 2, each). - Fatal adverse reactions occurred in 2.1% of patients; fatal adverse reactions included COVID-19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). - Permanent discontinuation due to an adverse reaction occurred in 4.7% of patients who received Retevmo. Adverse reactions resulting in permanent discontinuation were edema, multiple organ dysfunction syndrome, sudden death, and AST increased, diabetic ketoacidosis, chronic kidney disease, retinopathy, COVID-19 and somatic symptom disorder (n = 1, each). - Dosage interruptions due to an adverse reaction occurred in 49% of patients who received Retevmo. Adverse reactions requiring dosage omission in ≥5% of patients included ALT increased (9%) and hypertension (7%). - Dose reductions due to an adverse reaction occurred in 39% of patients who received Retevmo. One adverse reaction, increased ALT (7%), required a dose reduction in ≥5% of patients. - The most common adverse reactions (≥25%) in patients who received Retevmo were hypertension, edema, dry mouth, fatigue, diarrhea. - The most common Grade 3 or 4 laboratory abnormalities (≥5%) in patients who received Retevmo were decreased lymphocyte, increased ALT, decreased neutrophils, increased ALP, increased blood creatinine, decreased calcium, and increased AST. - Clinically relevant adverse reactions in ≤10% of patients who received Retevmo include dizziness (8%); urinary tract infections (8%); vomiting (8%); pneumonia, interstitial lung disease/pneumonitis, chylous ascites and hypersensitivity (all < 2%). For complete details on adverse reactions and laboratory abnormalities, please see full Prescribing Information. AE=adverse event; ALT=alanine transaminase; AST=aspartate aminotransferase; COVID-19=coronavirus disease 2019; GGT=gamma-glutamyl transferase; INR=international normalized ratio; LFT=liver function test; WBC=white blood cell **Select Important Safety Information** Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. ## L-001 Efficacy Summary **In patients with _RET_-mutant advanced or metastatic MTC** **Retevmo was granted initial approval based on LIBRETTO-001, a Phase I/II trial** Efficacy in cabozantinib/vandetanib-naive patients (n=88)1,3 ![Overall Response Rate and Median Duration of Response for Retevmo in cabozantinib/vandetanib-naive patients](https://retevmo.lilly.com/assets/img/c-se-us-0311_mtc-efficacy-summary_desktop-01.png) Up View description Graphic showing Objective Response Rate and Median Duration of Response for Retevmo treatment in cabozantinib/vandetanib-naive patients. ORR was 81% (95% CI: 71, 88), with 28% complete response (CR) and 52% PR (partial response). Median DoR not yet reached (95% CI: 51.3, NE). Median follow-up was 44.2 months. Due to rounding, percentages presented may not add up to the indicated totals. Major efficacy outcome measures for patients previously treatedǁ with cabozantinib and/or vandetanib (n=55)1: - ORR = 76% (95% CI: 63, 87) - 18% CR + 58% PR - Median DoR = 45.3 months (95% CI: 29.9, NE); Median follow-up: 50.7 months3 **Time-to-event endpoints are not interpretable in a single-arm study. The clinical significance of this descriptive analysis is not known.** ORR was defined as CR + PR and was assessed by IRC according to RECIST v1.1.1 All results reviewed by an IRC.1 Due to rounding, percentages presented may not add up to the indicated totals. ǁThe efficacy of Retevmo was evaluated in 55 patients with _RET_-mutant advanced MTC who were previously treated with cabozantinib or vandetanib enrolled into a cohort of LIBRETTO-001.1 ## L-001 Trial Design The phase I/II, multicohort, open-label, single-arm, multicenter LIBRETTO-001 trial included a pooled safety population of 796 patients with locally advanced or metastatic _RET_ fusion-positive NSCLC¶, advanced or metastatic _RET_ fusion-positive thyroid cancer (non-MTC)#, advanced or metastatic _RET_-mutant MTC, and other cancers, including patients with _RET_ alterations in other tumors\*\*. Major efficacy outcomes were ORR and DoR, and were evaluated in 565 patients. Other efficacy outcomes, evaluated in subsets of patients, included CNS ORR, CNS DoR, PFS, OS, time to response, and best change in tumor size from baseline. In phase II, the dose for Retevmo was 160 mg PO BID.1,4 ¶Patients with locally advanced or metastatic _RET_ fusion-positive NSCLC who had progressed on platinum-based chemotherapy and those without prior systemic therapy were enrolled in separate cohorts.1 #Non-MTC by histology included papillary (n=54), poorly differentiated (n=6), anaplastic (n=4), and Hurthle cell (n=1).1 \*\*Other tumors included pancreatic adenocarcinoma (n=11), colorectal cancer (n=10), and salivary cancer (n=4).1 CNS=central nervous system; PO=orally. **Select Important Safety Information** **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. **References: 1.** Retevmo (selpercatinib). Prescribing Information. Lilly USA, LLC. **2.** Hadoux J, Elisei R, Brose MS, et al. Phase 3 trial of selpercatinib in advanced _RET_-mutant medullary thyroid cancer. _N Engl J Med_. 2023;389(20):1851-1861. doi:10.1056/NEJMoa2309719 **3.** Data on File, Lilly USA, LLC. DOF-SE-US-0089. **4.** Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, _RET_ fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). https://clinicaltrials.gov/ct2/show/NCT03157128. Updated June 9, 2022. Accessed June 14, 2022. Important Safety Information and Indication or Indications. Select to Expand. IMPORTANT SAFETY INFORMATION INDICATIONS Important Safety Information. Select to Expand. IMPORTANT SAFETY INFORMATION ## IMPORTANT SAFETY INFORMATION ### **Hepatotoxicity:** Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal **interstitial lung disease (ILD)/pneumonitis** can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. **Hypertension** occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent **QT interval prolongation**. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, **hemorrhagic events** can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. **Hypersensitivity** occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. **Tumor lysis syndrome (TLS)** occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. **Impaired wound healing** can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause **hypothyroidism**. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause **fetal harm** when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. **Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients** (SCFE/SUFE) occurred in 1 adolescent (3.7% of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient (0.5% of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. **Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001** were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were vomiting (7%), constipation (7%), increased weight (7%), nausea (3.7%), and hemorrhage (3.7%). **Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%). **Severe adverse reactions (Grade 3-4) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531 were** (Retevmo vs cabozantinib / vandetanib) hypertension (19% vs 18%), electrocardiogram QT prolonged (4.7% vs 2.1%), fatigue (4.1% vs 9%), diarrhea (3.1% vs 8%), rash (1.6% vs 4.1%), pyrexia (1.0% vs 0%), nausea (1.0% vs 5%), dry mouth (0.5% vs 1.0%), abdominal pain (0.5% vs 2.1%), stomatitis (0.5% vs 13%), headache (0.5% vs 0%), and decreased appetite (0.5% vs 5%). **Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001.** The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. **Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001;** fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-121.** The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. **Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431.** The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. **Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431;** fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each). **Serious adverse reactions occurred in 22% of patients who received Retevmo in LIBRETTO-531.** The most frequent serious adverse reactions were pneumonia and pyrexia (n=3 each), and hypertension and urinary tract infection (n=2 each). **Fatal adverse reactions occurred in 2.1% of patients who received Retevmo in LIBRETTO-531;** fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death (n=1 each). **Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001,** were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-121** were musculoskeletal pain (56%), diarrhea (41%), headache (33%), nausea (30%), vomiting (30%), coronavirus infection (30%), abdominal pain (26%), fatigue (26%), pyrexia (26%), hemorrhage (26%), upper respiratory tract infection (22%), oropharyngeal pain (22%), cough (22%), hypothyroidism (19%), constipation (19%), edema (19%), increased weight (19%), rash (19%), stomatitis (15%), and proteinuria (15%). **Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%). **Common adverse reactions (all grades) occurring in ≥10% of patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were hypertension (43% vs 41%), edema (33% vs 5%), dry mouth (32% vs 10%), fatigue (28% vs 47%), diarrhea (26% vs 61%), headache (23% vs 21%), rash (19% vs 27%), abdominal pain (18% vs 21%), constipation (16% vs 12%), erectile dysfunction (16% vs 0%), stomatitis (14% vs 42%), electrocardiogram QT prolonged (14% vs 13%), pyrexia (12% vs 2.1%), decreased appetite (12% vs 28%), hypothyroidism (11% vs 21%), and nausea (10% vs 32%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001,** were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). **Laboratory abnormalities (all grades ≥15%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121** were decreased calcium (59%; 7%), increased ALT (56%; 3.7%), increased alkaline phosphatase (52%; 0%), increased AST (48%; 3.7%), decreased albumin (44%; 0%), decreased neutrophils (44%; 7%), increased bilirubin (30%; 0%), decreased lymphocytes (24%; 4.8%), increased creatinine (22%, 0%), decreased potassium (22%; 3.7%), decreased platelets (22%; 0%), decreased hemoglobin (19%; 7%), and decreased magnesium (15%; 3.7%). **Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431** were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%). **Laboratory abnormalities (all grades ≥5%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531** (Retevmo vs cabozantinib / vandetanib) were decreased calcium (55%; 5% vs 62%; 11%), increased ALT (53%; 16% vs 72%; 7%), increased AST (47%; 5% vs 68%; 3.2%), decreased lymphocytes (41%; 18% vs 36%; 13%), increased alkaline phosphatase (37%; 6% vs 28%, 5%), increased bilirubin (32%; 1.1% vs 30%; 3.2%), decreased neutrophils (33%; 14% vs 42%; 19%), decreased platelets (28%; 1.1% vs 34%; 1.1%),increased creatinine (27%; 6% vs 16%; 8%), decreased sodium (20%; 3.2% vs 16%; 0%), decreased hemoglobin (18%; 2.1% vs 23%; 2.1%), decreased albumin (11%; 1.1% vs 7%; 0), magnesium decreased (9%; 3.3% vs 26%; 9%), and decreased potassium (8%; 0% vs 22%; 4.4%). Concomitant use of **acid-reducing agents** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of **strong and moderate CYP3A inhibitors** increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of **strong and moderate CYP3A inducers** decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with **CYP2C8 and CYP3A substrates** increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with **P-gp or BCRP substrates** increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling. **The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age.** The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation who require systemic therapy, advanced or metastatic thyroid cancer with a _RET_ gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a _RET_ gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in **pediatric patients.** Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with **mild to severe renal impairment** (estimated Glomerular Filtration Rate \[eGFR\] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with **severe hepatic impairment** (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_18DEC24 **Please see full** **[Prescribing Information](http://uspl.lilly.com/Retevmo/Retevmo.html?s=pi)** **for Retevmo.** Indication or Indications. Select to Expand. INDICATIONS ## INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: - adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a _rearranged during transfection_ ( _RET_) gene fusion, as detected by an FDA-approved test - adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a _RET_ mutation, as detected by an FDA-approved test, who require systemic therapy - adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a _RET_ gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) - adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a _RET_ gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\* \*This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ## For Healthcare Professionals The information contained in **www.Retevmo.com/hcp** is technical in nature and intended for healthcare professionals in the United States only. If you are a US healthcare professional, click the “Continue” button below. **Yes, I am a US healthcare professional and would like to** **continue.** Go back [Continue](https://retevmo.lilly.com/) ## Specialty Pharmacy List # Specialty Pharmacy Network These contracted specialty pharmacies\* can fill a Retevmo prescription. | | | | | --- | --- | --- | | SPECIALTYPHARMACY | PHONENUMBER | FAX NUMBER | | Accredo | 1-877-732-3431 | 1-888-302-1028 | | AllianceRx Walgreens Prime | 1-888-347-3416 | 1-877-231-8302 | | Biologics | 1-800-850-4306 | 1-800-823-4506 | | BioPlus Specialty Pharmacy | 1-888-292-0744 | 1-800-269-5493 | | CVS Specialty | 1-888-280-1193 | 1-855-296-0210 | | CenterWell Specialty Pharmacy | 1-800-486-2668 | 1-877-405-7940 | | Onco360 Specialty Pharmacy | 1-877-662-6633 | 1-877-662-6355 | | Optum Specialty Pharmacy | 1-877-445-6874 | 1-877-342-4596 | Lilly is not affiliated with these specialty pharmacies and cannot endorse non-affiliated entities. The list presented above is for information purposes only. Retevmo can be purchased through authorized specialty distributors. To find the complete list of authorized specialty distributors, please visit [www.lillytrade.com](http://www.lillytrade.com/). # Please see full Prescribing Information for Retevmo. \*Current as of 02/2025. Please go to [https://www.retevmo.com](https://www.retevmo.com/) for the most up-to-date information. Retevmo® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. PP-SE-US-1567 2/2025  Lilly USA, LLC 2025. All rights reserved. ## Retevmo Tablet Information # Retevmo®: now in tablet form with four dose strengths Retevmo is switching from capsules to tablets, including more dose strengths. Retevmo capsules are offered in 40 mg and 80 mg strengths; Retevmo tablets are offered in 40 mg, 80 mg, 120 mg, and 160 mg strengths. # What’s changing? ![](https://retevmo.lilly.com/assets/pdf/images/ecaa871d8a528c51924b01581e2bba014ffe7186e08bff0d4e9c28b85b4188e4.jpg) aWhile Retevmo dosing recommendation remains twice daily, patients may be able to take a lower pill count at each dose interval. Tablet and capsule renderings shown may vary in size and color compared to actual tablets and capsules. Color, size, and texture may differ slightly due to differences in digital screen settings and/or printer capabilities Please note that for a period of time, patients may receive either the original capsule formulation or the reformulated Retevmo tablets, based on Specialty Pharmacy inventory. # How to take Retevmo How often should I take Retevmo? Take Retevmo exactly as your doctor tells you. Your doctor may change your dose, if needed. Do not change your dose or stop taking Retevmo without talking to your doctor. If I’m taking other medicines, do these medicines affect how I take Retevmo? • If you take: • a proton-pump inhibitor, take Retevmo with food. Examples of PPIs include dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole • an H2 blocker, take Retevmo 2 hours before or 10 hours after taking the H2 blocker. Examples of H2 blockers include famotidine, nizatidine, and cimetidine • an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take Retevmo 2 hours before or 2 hours after taking the antacid # What should I do if I miss a dose or get sick after taking a dose? Do not take a missed dose of Retevmo unless it is more than 6 hours until your next scheduled dose. If you get sick after taking a dose, do not take an extra dose, and take your next dose at your regular time In the event that you take too much Retevmo, call your doctor or go to the nearest hospital emergency room right away. If you have questions about Retevmo or need more information on how to take it, you should talk to your doctor. You can also call Lilly Support Services at 1-800-LillyRx # INDICATIONS AND SAFETY SUMMARY RETEVMO® (reh-TEHV-moh) is used to treat certain cancers caused by abnormal RET genes in: • adults with locally advanced non-small cell lung cancer (NSCLC) or NSCLC that has spread. • adults and children 2 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who require a medicine by mouth or injection (systemic therapy). • adults and children 2 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy), and who have received radioactive iodine and it did not work or is no longer working. • adults and children 2 years of age and older with locally advanced solid tumors (cancers) or solid tumors that have spread, and have gotten worse (progressed) on or after other treatment or there are no satisfactory treatment options.\* Your healthcare provider will perform a test to make sure that RETEVMO is right for you. • It is not known if RETEVMO is safe and effective when used in children younger than 2 years of age for the treatment of: ◦ advanced MTC or MTC that has spread who require a medicine by mouth or injection. ◦ advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection, and have received radioactive iodine and it did not work or is no longer working. ◦ locally advanced solid tumors or solid tumors that have spread, and have gotten worse on or after other treatment or there are no satisfactory treatment options. • i n children for other conditions. \\* This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit of Retevmo for this use. # Warnings - RETEVMO may cause serious side effects, including: Liver problems: Liver problems (increased liver enzymes) can happen during treatment with RETEVMO and may sometimes be serious. Your healthcare provider will do blood tests before and during treatment with RETEVMO to check for liver problems. Tell your healthcare provider right away if you get any of the following symptoms of liver problems during treatment: • yellowing of your skin or the white part of your eyes (jaundice) • dark, “tea-colored” urine • sleepiness • bleeding or bruising • l oss of appetite • nausea or vomiting • pain on the upper right side of your stomach area Lung problems: RETEVMO may cause severe or life-threatening inflammation (swelling) of the lungs during treatment, that can lead to death. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including: • shortness of breath • cough • fever High blood pressure (hypertension): High blood pressure is common with RETEVMO. It may sometimes be severe. You should check your blood pressure regularly during treatment with RETEVMO. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you have increased blood pressure readings or get any symptoms of high blood pressure, including: • confusion • headaches • shortness of breath • dizziness • chest pain # Heart rhythm changes (QT prolongation). RETEVMO may cause very slow, very fast, or irregular heartbeats. Your healthcare provider may perform tests before and during treatment with RETEVMO to check the activity of your heart and the levels of body salts (electrolytes) and thyroidstimulating hormone (TSH) in your blood. Tell your healthcare provider right away if you get any of the following symptoms: • loss of consciousness • fainting • dizziness • a change in the way your heart beats (heart palpitations) # INDICATIONS AND SAFETY SUMMARY (cont'd) Bleeding problems: RETEVMO can cause bleeding, which can be serious and may lead to death. Tell your healthcare provider if you have any signs of bleeding during treatment, including: • vomiting blood or if your vomit looks like coffee-grounds • pink or brown urine • red or black stools that look like tar • coughing up blood or blood clots • unusual bleeding or bruising of your skin • menstrual bleeding that is heavier than normal • unusual vaginal bleeding • nose bleeds that happen often • drowsiness or difficulty being awakened • confusion • headache • change in speech Allergic reactions: RETEVMO can cause a fever, rash, or pain in muscles or joints, especially during the first month of treatment. Tell your healthcare provider if you get any of these symptoms. Tumor lysis syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have kidney failure, the need for dialysis treatment, and an abnormal heartbeat. TLS can lead to hospitalization. Your healthcare provider may do blood tests to check you for TLS. You should stay well hydrated during treatment with RETEVMO. Call your healthcare provider or get emergency medical help right away if you develop any of these symptoms during treatment with RETEVMO: • nausea • vomiting • weakness • swelling • shortness of breath • muscle cramps • seizures Risk of wound healing problems: Wounds may not heal well during treatment with RETEVMO. Tell your healthcare provider if you plan to have any surgery before or during treatment with RETEVMO. • You should stop taking RETEVMO at least 7 days before planned surgery. • Your healthcare provider should tell you when you may start taking RETEVMO again after surgery. Low thyroid hormone levels in your blood (hypothyroidism). Your healthcare provider will do blood tests to check your thyroid function before and during treatment with RETEVMO. Tell your healthcare provider right away if you develop signs or symptoms of low thyroid hormone levels, including: • weight gain • feeling cold • tiredness that worsens or does not go away • constipation Hip joint problems (slipped capital femoral epiphysis or slipped upper femoral epiphysis) in children. Tell your healthcare provider right away if you develop sign and symptoms of hip problems, including hip or knee pain or a painless limp. # Common side effects The most common side effects of RETEVMO in adults with solid tumors include: • swelling of your arms, legs, hands, and feet (edema) • diarrhea • tiredness • dry mouth • stomach-area (abdominal) pain • constipation • rash • nausea • headache The most common side effects of RETEVMO in children 2 years and older with solid tumors include: • muscle and bone pain • diarrhea • headache • nausea • vomiting • coronavirus infection • stomach-area (abdominal) pain • tiredness • fever • bleeding The most common severe abnormal laboratory test results with RETEVMO in adults with solid tumors include decreased white blood cell count, increased liver enzymes, decreased levels of sodium in the blood, and decreased levels of calcium in the blood. The most common severe abnormal laboratory test results with RETEVMO in children 2 years and older with solid tumors include decreased levels of calcium in the blood, decreased red blood cell count, and decreased white blood cell count. RETEVMO may affect the ability to have children for both females and males. Talk to your healthcare provider if you want to have children and you are thinking about starting treatment with RETEVMO. • RETEVMO can harm your unborn baby. You should not become pregnant during treatment with RETEVMO. # • If you are able to become pregnant: ◦ Your healthcare provider will do a pregnancy test before you start treatment with RETEVMO. ◦ You should use effective birth control (contraception) during treatment and for 1 week after your last dose of RETEVMO. Talk to your healthcare provider about birth control methods that may be right for you. ◦ Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RETEVMO. • Males with partners who are able to become pregnant should use effective birth control during treatment with RETEVMO and for 1 week after your last dose of RETEVMO. These are not all the possible side effects with RETEVMO. If you are concerned about side effects, talk to your doctor. Tell your doctor about any side effects you have. You can also report side effects at 1-800-FDA-1088 or [www.fda.gov/medwatch](http://www.fda.gov/medwatch). # Before using Before taking RETEVMO, tell your healthcare provider about all your medical conditions, including if you: • have liver problems • have lung or breathing problems other than lung cancer • have high blood pressure • have heart problems, including a condition called QT prolongation • have bleeding problems • plan to have surgery. You should stop taking RETEVMO at least 7 days before your planned surgery. • are pregnant or plan to become pregnant. See section above for additional information. • are breastfeeding or plan to breastfeed. It is not known if RETEVMO passes into your breast milk. Do not breastfeed during treatment with RETEVMO and for 1 week after your last dose. Also tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RETEVMO may affect the way other medicines work and other medicines may affect how RETEVMO works, and may increase your risk of side effects. • During treatment with RETEVMO, you should avoid taking: ◦ St. John’s wort, ◦ proton-pump inhibitors (PPIs) such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, and rabeprazole, ◦ H2 blockers such as famotidine, nizatidine, and cimetidine, ◦ antacids that contain aluminum, magnesium, calcium, simethicone, or buffered medicines. If you cannot avoid taking PPIs, H2 blockers, or antacids, see the “How to take with certain other medicines” section below for more information. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. # How to take RETEVMO • Take RETEVMO exactly as your healthcare provider tells you. • Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with RETEVMO if you have side effects. Do not change your dose or stop taking RETEVMO unless your healthcare provider tells you. • Swallow RETEVMO capsules and tablets whole. Do not break, crush, or chew. • Do not give RETEVMO capsules to your child if they are unable to swallow a capsule. • Take RETEVMO with or without food. # INDICATIONS AND SAFETY SUMMARY (cont'd) • If you vomit after taking a dose of RETEVMO, do not take an extra dose. Take the next dose of RETEVMO at your scheduled time. • Do not take a missed dose of RETEVMO unless it is more than 6 hours until your next scheduled dose. • If you take too much RETEVMO, call your healthcare provider or go to the nearest hospital emergency room right away. # How to take RETEVMO with certain other medicines • If you take a PPI (such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole sodium, or rabeprazole), take RETEVMO with food. • If you take an H2 blocker (such as famotidine, nizatidine, or cimetidine), take RETEVMO 2 hours before or 10 hours after taking the H2 blocker. • If you take an antacid that contains aluminum, magnesium, calcium, simethicone, or buffered medicines, take RETEVMO 2 hours before or 2 hours after taking the antacid. # Learn more RETEVMO is a prescription medicine available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, $1 2 0 { \\mathrm { ~ m g } }$ , and 160 mg tablets. For more information, call 1-800-545-5979 or go to [www.Retevmo.com](http://www.retevmo.com/). This summary provides basic information about RETEVMO. It does not include all information known about this medicine. Read the information that comes with your medicine each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other health care provider about RETEVMO and how to take it. Your doctor is the best person to help you decide if RETEVMO is right for you. SE CON BS ALL 27SEP2024 ## Medical Necessity Letter Guide # Composing a Letter of Medical Necessity The following information is presented for informational purposes only and is not intended to provide reimbursement or legal advice. Laws, regulations, and policies concerning reimbursement are complex and are updated frequently. Eli Lilly and Company does not guarantee success in obtaining insurance payments. While we have made an effort to be current as of the issue date of this document, the information may not be as current or comprehensive when you view it. Providers are encouraged to contact third-party payers for specific information on their coverage policies. For more information, please call Lilly Support Services™ at 1-800-LillyRx (1-800-545-5979). Many health plans require that a Letter of Medical Necessity accompanies a Coverage Authorization Appeals Letter.\* The purpose of a Letter of Medical Necessity is to explain the prescribing healthcare provider’s (HCP’s) rationale and clinical decision making when choosing a treatment. This resource, Composing a Letter of Medical Necessity, provides information on the process of drafting a Letter of Medical Necessity. Included on the following page is a list of considerations, which can be followed when creating a Letter of Medical Necessity. In addition, two sample letters are attached to this document and include information that plans often require. Note that some plans have specific Coverage Authorization Forms that must be used to document a Letter of Medical Necessity. Also see Preparing a Coverage Authorization Appeals Letter for more information. Follow the patient’s plan requirements when requesting Retevmo®, otherwise treatment may be delayed. \*For Medicare beneficiaries, specific requirements must be met for the HCP to be considered a legal representative of the patient in an appeal For additional information, please visit [https://www.cms.gov/Medicare/CMS-Forms/CMS-Forms/downloads/cms1696.pdf](https://www.cms.gov/Medicare/CMS-Forms/CMS-Forms/downloads/cms1696.pdf). # INDICATIONS Retevmo is a kinase inhibitor indicated for the treatment of: • adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfectio (RET) gene fusion, as detected by an FDA-approved test • adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy • adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) • adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options† †This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. # SELECT IMPORTANT SAFETY INFORMATION FOR RETEVMO Hepatotoxicity: Serious hepatic adverse reactions occurred in $3 %$ of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in $59 %$ of patients, including Grade 3 or 4 events in $11 %$ and increased alanine aminotransferase (ALT) occurred in $5 5 %$ of patients, including Grade $3 \\mathsf { o r } 4$ events in $12 %$ . Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. # Composing a Letter of Medical Necessity # Letter of Medical Necessity Considerations 1. Include the patient’s full name, date of birth, plan identification number, and case identification number if a decision has already been rendered. 2. Provide a copy of the patient’s records with the following details: patient’s history (including relevant clinical and progress notes), diagnosis with specific International Classification of Diseases (ICD) code, and condition. 3. Supply diagnostic testing results to confirm RET gene fusion or RET mutation positivity that identifies the patient as a candidate for Retevmo. 4. Note the severity of the patient’s condition. 5. Document prior treatments, the duration of each, and the rationale for discontinuation. It may be beneficial to include Common Procedural Terminology (CPT)-4 and/or J-codes to define prior services/treatments, so that the health plan can conduct research and make a timely determination. 6. Attach clinical documentation that supports your recommendation; this information may be found in the Retevmo Prescribing Information and/or clinical peer-reviewed literature. # Sample Letter of Medical Necessity HCPs can follow this format for patients who are NOT currently receiving treatment with Retevmo (selpercatinib). \[Date\] \[Medical Director\] \[Name of Health Plan\] \[Mailing Address\] Re: \[Patient’s Name\] \[Plan Identification Number\] \[Date of Birth\] \[Case Identification\] # To whom it may concern: I am writing to provide additional information to support my claim for \[patient’s name\]’s treatment of \[locally advanced or metastatic NSCLC with a RET gene fusion, as detected by an FDA-approved test OR advanced or metastatic MTC with a RET mutation, as detected by an FDA-approved test, in patients who require systemic therapy OR advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, in patients who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) OR locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\] with Retevmo® (selpercatinib). In brief, treatment with Retevmo \[dose, frequency\] is medically appropriate and necessary for this patient. This letter outlines the patient’s medical history and previous treatments to support my recommendation for treatment with Retevmo. # Patient’s history, diagnosis, condition, and symptoms\*: Patient must have a diagnosis for an indication of Retevmo. Retevmo is a kinase inhibitor indicated for the treatment of: • adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test • adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy • adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) • adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options† †This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ![](https://retevmo.lilly.com/assets/pdf/images/c89451cbf8026041c3bdeacd140e4779a823347ae3b22d1b47c590d820624150.jpg) \[Provide clinical rationale for this treatment; this information may be found in the Retevmo prescribing information and/or clinical peer-reviewed literature.\] \[Insert your recommendation summary here, including your professional opinion of the patient’s likely prognosis or disease progression without treatment with Retevmo.\] Please feel free to contact me, \[HCP’s name\], at \[office phone number\] for any additional information you may require. I look forward to receiving your timely response and approval of this claim. Sincerely, \[Physician’s name and signature\] \[Physician’s medical specialty\] \[Physician’s NPI\] \[Physician’s practice name\] \[Phone #\] \[Fax #\] \[Patient’s name and signature\] Encl: Medical records Clinical trial information # Sample Letter of Medical Necessity HCPs can follow this format for patients who HAVE been treated with Retevmo (selpercatinib) and have had treatment interruptions. \[Date\] \[Medical Director\] \[Name of Health Plan\] \[Mailing Address\] Re: \[Patient’s Name\] \[Plan Identification Number\] \[Date of Birth\] \[Case Identification\] To whom it may concern: I am writing to provide additional information to support my claim for \[patient’s name\]’s treatment of \[locally advanced or metastatic NSCLC with a RET gene fusion, as detected by an FDA-approved test, OR advanced or metastatic MTC with a RET mutation, as detected by an FDA-approved test, in patients who require systemic therapy OR advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, in patients who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) OR locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options\] with Retevmo® (selpercatinib). In brief, treatment with Retevmo \[dose, frequency\] is medically appropriate and necessary for this patient. This letter outlines the patient’s medical history and previous treatments to support my recommendation for treatment with Retevmo. \[In this section, describe the severity of advanced cancer at the time when the patient was first prescribed Retevmo. In addition, include a summary of the patient’s clinical response to Retevmo and list improvements (if any) in clinical presentation since treatment began.\] # Patient’s history, diagnosis, condition, and symptoms\*: Patient must have a diagnosis for an indication of Retevmo. Retevmo is a kinase inhibitor indicated for the treatment of: • adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test • adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy • adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) • adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, a detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options† †This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. ![](https://retevmo.lilly.com/assets/pdf/images/95aea23aec65cbd4b9c509be63a062acd763e1239617fe059109a46d7fc3cd44.jpg) \[Provide clinical rationale for this treatment; this information may be found in the Retevmo prescribing information and/or clinical peer-reviewed literature.\] \[Insert your recommendation summary here, including your professional opinion of the patient’s likely prognosis o disease progression without treatment with Retevmo.\] Please feel free to contact me, \[HCP’s name\], at \[office phone number\] for any additional information you may require. I look forward to receiving your timely response and approval of this claim. Sincerely, \[Patient’s name and signature\] Encl: Medical records Clinical trial information \[Physician’s name and signature\] \[Physician’s medical specialty\] \[Physician’s NPI\] \[Physician’s practice name\] \[Phone #\] \[Fax #\] \*Include patient’s medical records and supporting documentation. ‡Identify drug name, strength, dosage form, and therapeutic outcome. # IMPORTANT SAFETY INFORMATION FOR RETEVMO® (selpercatinib) Hepatotoxicity: Serious hepatic adverse reactions occurred in $3 %$ of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in $5 9 %$ of patients, including Grade 3 or 4 events in $11 %$ and increased alanine aminotransferase (ALT) occurred in $5 5 %$ of patients, including Grade 3 or 4 events in $12 %$ . Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with Retevmo. ILD/ pneumonitis occurred in $1 . 8 %$ of patients who received Retevmo, including $0 . 3 %$ with Grade 3 or 4 events, and $0 . 3 %$ with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. Hypertension occurred in $41 %$ of patients, including Grade 3 hypertension in $20 %$ and Grade 4 in one $( 0 . 1 % )$ patient. Overall, $6 . 3 %$ had their dose interrupted and $1 . 3 %$ had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent QT interval prolongation. An increase in QTcF interval to $> 5 0 0$ ms was measured in $7 %$ of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in $20 %$ of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, hemorrhagic events can occur with Retevmo. Grade $\\geq 3$ hemorrhagic events occurred in $3 . 1 %$ of patients treated with Retevmo including 4 $( 0 . 5 % )$ patients with fatal hemorrhagic events, including cerebral hemorrhage $( n = 2 )$ , tracheostomy site hemorrhage $( \\mathsf { n } { = } 1 )$ , and hemoptysis $( \\mathsf { n } { = } 1 )$ . Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. Hypersensitivity occurred in $6 %$ of patients receiving Retevmo, including Grade 3 hypersensitivity in $1 . 9 %$ . The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. Tumor lysis syndrome (TLS) occurred in $0 . 6 %$ of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause hypothyroidism. Hypothyroidism occurred in $1 3 %$ of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in $1 3 %$ of patients (50/373) with thyroid cancer and $1 3 %$ of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. # MPORTANT SAFETY INFORMATION FOR RETEVMO® (selpercatinib) (CONTINUED) Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of $1 6 0 ~ \\mathsf { m g }$ twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. Slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients (SCFE/SUFE) occurred in 1 adolescent $3 . 7 %$ of 27 patients) receiving Retevmo in LIBRETTO-121 and 1 adolescent patient $0 . 5 %$ of 193 patients) receiving Retevmo in LIBRETTO-531. Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate. Severe adverse reactions (Grade 3-4) occurring in $2 2 0 %$ of patients who received Retevmo in LIBRETTO-001 were hypertension $20 %$ , diarrhea $( 5 % )$ , prolonged QT interval $( 4 . 8 % )$ , dyspnea $( 3 . 1 % )$ , fatigue $( 3 . 1 % )$ , hemorrhage $( 2 . 6 % )$ , abdominal pain $( 2 . 5 % )$ , vomiting $( 1 . 8 % )$ , headache $( 1 . 4 % )$ , nausea $( 1 . 1 % )$ , constipation $( 0 . 8 % )$ , edema $( 0 . 8 % )$ , rash $( 0 . 6 % )$ , and arthralgia $( 0 . 3 % )$ . Severe adverse reactions (Grade 3-4) occurring in $21 5 %$ of patients who received Retevmo in LIBRETTO-121 were vomiting $( 7 % )$ constipation $( 7 % )$ , increased weight $( 7 % )$ , nausea $( 3 . 7 % )$ , and hemorrhage $( 3 . 7 % )$ . Severe adverse reactions (Grade 3-4) occurring in $21 5 %$ of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were hypertension ( $20 %$ vs $3 . 1 %$ , electrocardiogram QT prolonged $9 %$ vs $0 %$ , fatigue $3 . 2 %$ vs $5 %$ ), edema $2 . 5 %$ vs $0 %$ ), rash $1 . 9 %$ vs $1 . 0 %$ , diarrhea $1 . 3 %$ vs $2 . 0 %$ , abdominal pain $0 . 6 %$ vs $2 . 0 %$ , pyrexia $( 0 . 6 %$ vs $0 %$ ), COVID19 infection $0 . 6 %$ vs $0 %$ , constipation $0 %$ vs $1 . 0 %$ , nausea $0 %$ vs $1 . 0 %$ , vomiting $0 %$ vs $1 . 0 %$ ), and decreased appetite ( $0 %$ vs $2 . 0 %$ ). Severe adverse reactions (Grade 3-4) occurring in $2 1 0 %$ of patients who received Retevmo in LIBRETTO-531 were (Retevmo vs cabozantinib / vandetanib) hypertension $1 9 %$ vs $1 8 %$ ), electrocardiogram QT prolonged $4 . 7 %$ vs $2 . 1 %$ , fatigue $4 . 1 %$ vs $9 %$ ), diarrhea $3 . 1 %$ vs $8 %$ ), rash $1 . 6 %$ vs $4 . 1 %$ ), pyrexia $1 . 0 %$ vs $0 %$ , nausea $1 . 0 %$ vs $5 %$ ), dry mouth $( 0 . 5 %$ vs $1 . 0 %$ ), abdominal pain $0 . 5 %$ vs $2 . 1 %$ ), stomatitis $0 . 5 %$ vs $1 3 %$ ), headache $0 . 5 %$ vs $0 %$ ), and decreased appetite $( 0 . 5 %$ vs $5 %$ ). Serious adverse reactions occurred in $44 %$ of patients who received Retevmo in LIBRETTO-001. The most frequently reported serious adverse reactions (in $2 2 %$ of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. Fatal adverse reactions occurred in $3 %$ of patients in LIBRETTO-001; fatal adverse reactions included sepsis $( n = 6 )$ , respiratory failure $( n = 5 )$ ), hemorrhage $( n = 4 )$ , pneumonia $( n = 3 )$ , pneumonitis $( n = 2 )$ ), cardiac arrest $( n = 2 )$ ), sudden death $( \\mathsf { n } = 1 )$ , and cardiac failure $( \\mathsf { n } = 1 )$ ). Serious adverse reactions occurred in $22 %$ of patients who received Retevmo in LIBRETTO-121. The serious adverse reactions (in 1 patient each) were abdominal infection, abdominal pain, aspiration, constipation, diarrhea, epiphysiolysis, nausea, pneumonia, pneumatosis intestinalis, rhinovirus infection, sepsis, and vomiting. Serious adverse reactions occurred in $3 5 %$ of patients who received Retevmo in LIBRETTO-431. The most frequently reported serious adverse reactions $1 \\geq 2 %$ of patients) were pleural effusion and abnormal hepatic function. Fatal adverse reactions occurred in $4 . 4 %$ of patients who received Retevmo in LIBRETTO-431; fatal adverse reactions included myocardial infarction $( n = 2 )$ , respiratory failure $( n = 2 )$ ), cardiac arrest, malnutrition, and sudden death $\\mathrm { \\Delta } \_ { \\mathrm { n } = 1 }$ each). Serious adverse reactions occurred in $22 %$ of patients who received Retevmo in LIBRETTO-531. The most frequent serious adverse reactions were pneumonia and pyrexia $n = 3$ each), and hypertension and urinary tract infection $\\cdot n = 2$ each). Fatal adverse reactions occurred in $2 . 1 %$ of patients who received Retevmo in LIBRETTO-531; fatal adverse reactions included COVID19, diabetic ketoacidosis, multiple organ dysfunction syndrome, and sudden death $\\mathrm { \\Delta } \\cdot \\mathrm { n } { = } 1$ each). Common adverse reactions (all grades) occurring in $2 2 0 %$ of patients who received Retevmo in LIBRETTO-001, were edema $( 4 9 % )$ , diarrhea $( 4 7 % )$ , fatigue $( 4 6 % )$ , dry mouth $( 4 3 % )$ , hypertension $( 4 1 % )$ , abdominal pain $( 3 4 % )$ , rash $( 3 3 % )$ , constipation $( 3 3 % )$ , nausea $( 3 1 % )$ , headache $( 2 8 % )$ , cough $( 2 4 % )$ , vomiting $( 2 2 % )$ , dyspnea $( 2 2 % )$ ), hemorrhage $( 2 2 % )$ , arthralgia $( 2 1 % )$ , and prolonged QT interval $( 2 1 % )$ . Please see Important Safety Information continued on pages 7 and 8 and click for full Prescribing Information for Retevmo. # MPORTANT SAFETY INFORMATION FOR RETEVMO® (selpercatinib) (CONTINUED) Common adverse reactions (all grades) occurring in $2 1 5 %$ of patients who received Retevmo in LIBRETTO-121 were musculoskeletal pain $( 5 6 % )$ , diarrhea $( 4 1 % )$ , headache $( 3 3 % )$ , nausea $( 3 0 % )$ , vomiting $( 3 0 % )$ , coronavirus infection $( 3 0 % )$ , abdominal pain $( 2 6 % )$ , fatigue $( 2 6 % )$ , pyrexia $( 2 6 % )$ , hemorrhage $( 2 6 % )$ , upper respiratory tract infection $( 2 2 % )$ , oropharyngeal pain $( 2 2 % )$ , cough $( 2 2 % )$ , hypothyroidism $( 1 9 % )$ , constipation $( 1 9 % )$ , edema $( 1 9 % )$ , increased weight $( 1 9 % )$ , rash $( 1 9 % )$ , stomatitis $( 1 5 % )$ , and proteinuria $( 1 5 % )$ . Common adverse reactions (all grades) occurring in $2 1 5 %$ of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were hypertension ( $48 %$ vs $7 %$ ), diarrhea $44 %$ vs $24 %$ ), edema $41 %$ vs $2 8 %$ ), dry mouth ( $39 %$ vs $6 %$ ), rash $3 3 %$ vs $30 %$ ), fatigue $32 %$ vs $50 %$ ), abdominal pain $2 5 %$ vs $1 9 %$ ), musculoskeletal pain $2 5 %$ vs $28 %$ ), constipation ( $22 %$ vs $40 %$ ), electrocardiogram QT prolonged $20 %$ vs $1 . 0 %$ , COVID19 infection $1 9 %$ vs $1 8 %$ , stomatitis $1 8 %$ vs $1 6 %$ , decreased appetite $1 7 %$ vs $34 %$ ), nausea $1 3 %$ vs $44 %$ , vomiting $1 3 %$ vs $23 %$ ), and pyrexia $1 3 %$ vs $23 %$ ). Common adverse reactions (all grades) occurring in $2 1 0 %$ of patients who received Retevmo in LIBRETTO-531 (Retevmo vs cabozantinib / vandetanib) were hypertension $43 %$ vs $41 %$ , edema $3 3 %$ vs $5 %$ ), dry mouth ( $32 %$ vs $10 %$ , fatigue $2 8 %$ vs $47 %$ ), diarrhea $2 6 %$ vs $61 %$ ), headache $23 %$ vs $21 %$ ), rash $1 9 %$ vs $2 7 %$ , abdominal pain $1 8 %$ vs $21 %$ , constipation $1 6 %$ vs $12 %$ , erectile dysfunction $1 6 %$ vs $0 %$ ), stomatitis $14 %$ vs $42 %$ ), electrocardiogram QT prolonged $14 %$ vs $1 3 %$ ), pyrexia $12 %$ vs $2 . 1 %$ ), decreased appetite $12 %$ vs $2 8 %$ ), hypothyroidism $1 1 %$ vs $21 %$ , and nausea $10 %$ vs $32 %$ . Laboratory abnormalities (all grades $2 2 0 %$ ; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001, were increased AST $59 %$ ; $1 1 %$ ), decreased calcium $5 9 %$ ; $5 . 7 %$ , increased ALT $56 %$ ; $12 %$ ), decreased albumin $( 5 6 %$ ; $2 . 3 %$ , increased glucose $1 5 %$ ; $2 . 8 %$ ), decreased lymphocytes $1 5 2 %$ ; $20 %$ , increased creatinine $( 4 7 %$ ; $2 . 4 %$ ), decreased sodium $( 4 2 %$ ; $1 1 %$ , increased alkaline phosphatase $( 4 0 %$ ; $3 . 4 %$ ), decreased platelets $3 7 %$ ; $3 . 2 %$ , increased total cholesterol $3 5 %$ ; $1 . 7 %$ , increased potassium $34 %$ ; $2 . 7 %$ ), decreased glucose $34 %$ ; $1 . 0 %$ ), decreased magnesium ( $3 3 %$ ; $0 . 6 %$ , increased bilirubin $30 %$ ; $2 . 8 %$ ), decreased hemoglobin $2 8 %$ ; $3 . 5 %$ , and decreased neutrophils $2 5 %$ ; $3 . 2 %$ . Laboratory abnormalities (all grades $21 5 %$ ; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-121 were decreased calcium $5 9 %$ ; $7 %$ ), increased ALT $( 5 6 %$ ; $3 . 7 %$ , increased alkaline phosphatase $52 %$ ; $0 %$ ), increased AST $48 %$ ; $3 . 7 %$ , decreased albumin $44 %$ ; $0 %$ , decreased neutrophils $44 %$ ; $7 %$ , increased bilirubin $30 %$ ; $0 %$ ), decreased lymphocytes $24 %$ ; $4 . 8 %$ , increased creatinine $2 2 %$ , $0 %$ , decreased potassium $22 %$ ; $3 . 7 %$ ), decreased platelets ( $22 %$ ; $0 %$ , decreased hemoglobin $1 9 %$ ; $7 %$ , and decreased magnesium $1 5 %$ ; $3 . 7 %$ ). Laboratory abnormalities (all grades $2 2 0 %$ ; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were increased ALT $81 %$ ; $21 %$ vs $63 %$ ; $4 . 1 %$ ), increased AST $( 7 7 %$ ; $10 %$ vs $46 %$ ; $0 %$ ), decreased calcium $1 5 3 %$ ; $1 . 9 %$ vs $24 %$ ; $1 . 0 %$ ), decreased platelets $5 3 %$ ; $3 . 2 %$ vs $39 %$ ; $5 %$ ), decreased lymphocytes $1 5 3 %$ ; $8 %$ vs $64 %$ ; $1 5 %$ ), decreased neutrophils $1 5 3 %$ ; $2 . 0 %$ vs $58 %$ ; $1 1 %$ ), increased bilirubin $1 5 2 %$ ; $1 . 3 %$ vs $9 %$ ; $0 %$ ), increased alkaline phosphatase ( $3 5 %$ ; $1 . 3 %$ vs $22 %$ ; $0 %$ ), decreased sodium $31 %$ ; $3 . 2 %$ vs $41 %$ ; $2 . 1 %$ ), decreased albumin ( $2 5 %$ ; $0 %$ vs $5 %$ ; $0 %$ , increased blood creatinine $23 %$ ; $0 %$ vs $21 %$ ; $0 %$ ), decreased hemoglobin $21 %$ ; $0 %$ vs $91 %$ ; $5 %$ ), decreased potassium $( 1 7 %$ ; $1 . 3 %$ vs $1 5 %$ ; $1 . 0 %$ , and decreased magnesium $( 1 6 %$ ; $0 . 6 %$ vs $8 %$ ; $0 %$ . Laboratory abnormalities (all grades $\\ge 5 % ;$ ; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-531 (Retevmo vs cabozantinib / vandetanib) were decreased calcium $55 %$ ; $5 %$ vs $62 %$ ; $11 %$ ), increased ALT $5 3 %$ ; $1 6 %$ vs $72 %$ ; $7 %$ ), increased AST $47 %$ ; $5 %$ vs $68 %$ ; $3 . 2 %$ , decreased lymphocytes $41 %$ ; $1 8 %$ vs $3 6 %$ ; $1 3 %$ ), increased alkaline phosphatase $3 7 %$ ; $6 %$ vs $2 8 %$ $5 %$ , increased bilirubin $32 %$ ; $1 . 1 %$ vs $30 %$ ; $3 . 2 %$ ), decreased neutrophils $3 3 %$ ; $14 %$ vs $42 %$ ; $1 9 %$ ), decreased platelets $2 8 %$ ; $1 . 1 %$ vs $34 %$ ; $1 . 1 %$ ),increased creatinine $( 2 7 %$ ; $6 %$ vs $1 6 %$ ; $8 %$ , decreased sodium $20 %$ ; $3 . 2 %$ vs $1 6 %$ ; $0 %$ ), decreased hemoglobin $1 8 %$ ; $2 . 1 %$ vs $23 %$ ; $2 . 1 %$ ), decreased albumin ( $1 1 %$ ; $1 . 1 %$ vs $7 %$ ; 0), magnesium decreased $9 %$ ; $3 . 3 %$ vs $2 6 %$ ; $9 %$ ), and decreased potassium $8 %$ ; $0 %$ vs $22 %$ ; $4 . 4 %$ . Concomitant use of acid-reducing agents decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of strong and moderate CYP3A inhibitors increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Please see Important Safety Information continued on page 8 and click for full Prescribing Information for Retevmo. # MPORTANT SAFETY INFORMATION FOR RETEVMO® (selpercatinib) (CONTINUED) Concomitant use of strong and moderate CYP3A inducers decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) inhibitor. Concomitant use of Retevmo with P-gp substrates increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp substrates provided in their approved product labeling. The safety and effectiveness of Retevmo have not been established in pediatric patients less than 2 years of age. The safety and effectiveness of Retevmo have been established in pediatric patients 2 years of age and older for the treatment of advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation who require systemic therapy, advanced or metastatic thyroid cancer with a RET gene fusion who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate), and locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Monitor open growth plates in pediatric patients. Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with mild to severe renal impairment (estimated Glomerular Filtration Rate \[eGFR\] $\\geq 1 5$ to 89 mL/min, estimated by Modification of Diet in Renal Disease \[MDRD\] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times upper limit of normal \[ULN\] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets. SE HCP ISI All\_27SEP24