FDA Approves Selpercatinib for 3 RET-Positive Cancer Types

May 8, 2020

The FDA approved the first therapy to treat cancers with rearranged during transfection (RET) gene alterations.

The FDA approved selpercatinib (Retevmo), the first of its kind, to treat non-small cell lung cancer (NSCLC), medullary thyroid cancer and other types of thyroid cancers with rearranged during transfection, or RET, alterations.

Selpercatinib is indicated for the following:
• 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
• Advanced RET fusion-positive thyroid cancer in patients aged 12 and older that requires systemic therapy that has stopped responding to radioactive iodine therapy or is not appropriate for radioactive iodine therapy

The FDA made its decision based on results from a trial that evaluated the agent in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy; 143 patients with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both and patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib; and 19 patients with RET fusion-positive thyroid cancer who were radioactive iodine-refractory (RAI)) 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.

In the NSCLC study cohort of patients who received prior therapy, the agent demonstrated an objective response rate (ORR) of 68%, including a 2% complete response (CR) rate and a 66% partial response (PR) rate; the stable disease (SD) rate was 26%. In treatment-naïve patients, the ORR with selpercatinib was 85%. In the RET-mutant MTC cohort ho received prior treatment with cabozantinib (Cabometyx) or vandetanib, the ORR with selpercatinib was 56%; the CR rate was 6%, the PR rate was 51%, and 5% of patients developed progressive disease (PD).

The most common side effects with selpercatinib were increased aspartate aminotransferase (AST) and alanine aminotransferase 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, increased alkaline phosphatase, hypertension, fatigue, swelling in the body or limbs, low blood platelet count, increased cholesterol, rash, constipation and decreased sodium in the blood.

"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 Dr. Richard Pazdur, 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."