The US FDA has approved Retevmo (selpercatinib) capsules to treat three types of tumors – non-small cell lung cancer, medullary thyroid cancer and other types of thyroid cancers – in patients whose tumors have an alteration (mutation or fusion) in a specific gene (RET or “rearranged during transfection”). Retevmo is the first therapy approved specifically for cancer patients with the RET gene alterations. “Innovations in gene-specific therapies continue to advance the practice of medicine at a rapid pace and offer options to patients who previously had few,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “The FDA is committed to reviewing treatments like Retevmo that are targeted to specific subsets of patients with cancer.” Specifically, the cancers that Retevmo is approved to treat include: Non-small cell lung cancer (NSCLC) that has spread in adults,Advanced medullary thyroid cancer (MTC) or MTC that has spread, in patients 12 and older who require systemic therapy (a treatment option that spreads across the entire body, is not targeted), andAdvanced RET fusion-positive thyroid cancer in those age 12 and older that requires systemic therapy that has stopped responding to radioactive iodine therapy or is not appropriate for radioactive iodine therapy.Retevmo is a kinase inhibitor, meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing. Before beginning treatment, the identification of a RET gene alteration must be determined using laboratory testing. The FDA approved Retevmo on the results of a clinical trial involving patients with each of the three types of tumors. During the clinical trial, patients received 160 mg Retevmo orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR), which reflects the percentage of patients that had a certain amount of tumor shrinkage, and duration of response (DOR). Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR for the 105 patients was 64%. For 81% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had never undergone treatment. The ORR for these patients was 84%. For 58% of patients who had a response to the treatment, their response lasted at least six months. Efficacy for MTC in adults and pediatric patients was evaluated in those 12 years of age and older with RET-mutant MTC. The study enrolled 143 patients with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both (types of chemotherapy), and patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for the 55 previously treated patients was 69%. For 76% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 88 patients who had not been previously treated with an approved therapy for MTC. The ORR for these patients was 73%. For 61% of patients who had a response to the treatment, their response lasted at least six months. Efficacy for RET fusion-positive thyroid cancer was evaluated in adults and pediatric patients 12 years of age and older. The study enrolled 19 patients with RET fusion-positive thyroid cancer who were radioactive iodine-refractory (RAI, if an appropriate treatment option) and had received another prior systemic treatment, and eight patients with RET fusion-positive thyroid cancer who were RAI-refractory and had not received any additional therapy. The ORR for the 19 previously treated patients was 79%. For 87% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in eight patients who had not received therapy other than RAI. The ORR for these patients was 100%. For 75% of patients who had a response to the treatment, their response lasted at least six months. The most common side effects with Retevmo were increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes in the liver, increased blood sugar, decreased white blood cell count, decreased albumin in the blood, decreased calcium in the blood, dry mouth, diarrhea, increased creatinine (which can measure kidney function), increased alkaline phosphatase (an enzyme found in the liver and bones), hypertension, fatigue, swelling in the body or limbs, low blood platelet count, increased cholesterol, rash, constipation and decreased sodium in the blood. Retevmo can cause serious side effects including hepatotoxicity (liver damage or injury), elevated blood pressure, QT prolongation (the heart muscle takes longer than normal to recharge between beats), bleeding and allergic reactions. If a patient experiences hepatotoxicity, Retevmo should be withheld, dose reduced or permanently discontinued. Patients undergoing surgery should tell their doctor as drugs similar to Retevmo have caused problems with wound healing. Retevmo may cause harm to a developing fetus or a newborn baby. Health care professionals should advise pregnant women of this risk and should advise both females of reproductive potential and males patients with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for one week after the last dose. Additionally, women should not breastfeed while on Retevmo. Retevmo was approved under the Accelerated Approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally provide a meaningful advantage over existing treatments. The FDA also granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Additionally, Retevmo received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.