FDA Approves Selpercatinib for Certain Non–Small Cell Lung, Thyroid Cancers

The FDA approved Eli Lilly’s selpercatinib (Retevmo) capsules under an accelerated approval pathway to treat non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other thyroid cancer tumors. The treatment is indicated for patients whose tumors have an alternation, such as a mutation or fusion, in a specific gene (RET or ‘rearranged during transfection’), marking the first approval of a therapy for cancer patients with the RET gene alterations.

Selpercatinib is a kinase inhibitor which helps to prevent cancer cells from growing. Prior to beginning treatment, an RET gene mutation must be determined using laboratory testing. The treatment also received an orphan drug designation.

“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.

Specifically, selpercatinib is approved to treat:

• Metastatic NSCLC in adults
• 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

In a clinical trial, patients with all 3 types of tumors received 160 mg selpercatinib orally twice daily until disease progression or unacceptable toxicity. Efficacy was measured in overall response rates (ORR) based on the percentage of patients that exhibited tumor shrinkage and duration or response.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases," said Alexander Drilon, MD, acting chief of early drug development at Memorial Sloan Kettering Cancer Center and lead investigator of the trial.

Participants in all 3 cohorts were split into those who underwent previous chemotherapy and those for whom selpercatinib was the sole treatment. ORRs of each subgroup ranged from 55% to 100%.

In the trial, there was a 5% discontinuation rate due to adverse reactions. Common side effects (≥25 percent) included increased blood sugar, decreased white blood cell count, and hypertension, among others. The most serious side effects reported were hepatoxicity, elevated blood pressure, QT prolongation, bleeding and allergenic reactions. The treatment may also harm a developing fetus or newborn baby, and women are recommended not to breastfeed while taking selpercatinib.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy. I am pleased that patients with these RET-driven cancers have this newly approved option,” Drilon said.