The U.S. Food and Drug Administration (FDA) has approved the kinase inhibitor, Retevmo (selpercatinib), to treat people with three cancers that have a mutation or fusion in the RET gene. The three cancers are:
- Non-small cell lung cancer (NSCLC) that has spread
- 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 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.
This approval was largely based on a clinical trial involving the three patient populations listed above who received selpercatinib (160 mg capsules twice daily) until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response.
In adults with RET fusion-positive NSCLC who had previously been given chemotherapy (n=105), the ORR was 64% and of those patients, 81% had their response last at least six months. In treatment-naïve adults with RET fusion-positive NSCLC (n=39), the ORR was 84% and of those patients, 58% had their response last at least six months.
In adults and children, 12 years and older, with RET-mutant MTC who had previously been given chemotherapy (n=55), the ORR was 69% and of those patients, 76% had their response last at least six months. In treatment-naïve patients with RET-mutant MTC (n=88), the ORR was 73% and of those patients, 61% had their response last at least six months.
In adults and children, 12 years and older, with RET fusion-positive thyroid cancer who had previously been given chemotherapy and were radioactive-iodine refractory (n=19), the ORR was 79% and of those patients, 87% had their response last at least six months. In chemotherapy-naïve patients (n=8), the ORR was 100% and of those patients, 75% had their response last at least six months.
The most common side effects 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.
Selpercatinib can cause serious side effects including hepatotoxicity, elevated blood pressure, QT prolongation, bleeding and allergic reactions. If a patient experiences hepatotoxicity, treatment should be withheld, dose reduced or permanently discontinued.
Selpercatinib was approved under the Accelerated Approval pathway and its application was granted Priority Review and Breakthrough Therapy Designations. Selpercatinib also has an Orphan Drug Designation, which the FDA provides for drugs focused on rare conditions.