FDA Approval Insights: Selpercatinib in RET+ NSCLC and Thyroid Cancers

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Caroline Seymour.

OncLive® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Alexander Drilon, MD, research director of Early Drug Development at Memorial Sloan Kettering Cancer Center, to discuss the FDA approval of selpercatinib for the treatment of patients with RET alteration–positive non–small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and other thyroid cancers.

On May 8, 2020, the FDA granted an accelerated approval to selpercatinib, formally known as LOXO-292, for the treatment of adult patients with metastatic RET fusion–positive NSCLC; adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC who require systemic therapy; and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.

The approval was based on the results of the phase 1/2 multicenter, open-label, multicohort LIBRETTO-001 trial. The NSCLC cohort included 105 adult patients with RET fusion–positive NSCLC who had received prior platinum-based chemotherapy. In these patients, the objective response rate (ORR) was 64%, including a response lasting at least 6 months among 81% of responders. Among 39 treatment-naïve patients, the ORR was 84%; 58% of the responders had a response at least 6 months.

Regarding safety, the most common adverse effects (AEs) with selpercatinib included increased aspartate aminotransferase and alanine aminotransferase, increased blood sugar, decreased white blood cell count, decreased albumin in the blood, decreased calcium in the blood, dry mouth, and 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, were also reported.

The FDA also noted that selpercatinib can cause serious AEs, including hepatotoxicity, elevated blood pressure, QT prolongation, bleeding, and allergic reactions.

The accelerated approval of selpercatinib in lung cancer is contingent on the results of the confirmatory phase 3 LIBRETTO-431 trial, which is evaluating selpercatinib in patients with advanced or metastatic RET fusion–positive NSCLC. The confirmatory LIBRETTO-531 study is evaluating the agent in patients with RET-mutant MTC.

In our exclusive interview, Dr. Drilon provided background on use of targeted therapy in advanced NSCLC, discussed the frequency of RET alterations, and expanded on the data from the LIBRETTO-001 trial that led to the accelerated approval of selpercatinib.