FDA Approves Selpercatinib for RET-Mutant NSCLC, Thyroid Cancers

FDA Approves Selpercatinib for RET-Mutant NSCLC, Thyroid Cancers

The FDA approved selpercatinib (Retevmo) for the treatment of patients with non-small cell lung cancer (NSCLC), medullary thyroid cancer, and other types of thyroid cancers, that have a RET gene alteration. This is the first therapy approved specifically for patients with RET mutations/fusions.

The kinase inhibitor is approved to treat:

• Metastatic NSCLC in adults
• Advanced or metastatic medullary thyroid cancer in patients aged 12 or older who require systemic therapy
• Advanced RET fusion-positive thyroid cancer in patients 12 or older who require systemic therapy that has stopped responding to, or is not appropriate for, radioactive iodine therapy

“Innovations in gene-specific therapies continue to advance the practice of medicine at a rapid pace and offer options to patients previously had few,” 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, said in a statement.

The approval was based off a clinical trial involving groups of patients fitting the 3 indications. Participants received 160 mg daily of selpercatinib twice a day until disease progression or unacceptable toxicity. Main outcomes were overall response rate (ORR) and duration of response (DOR).

A total of 105 patients were evaluated on the NSCLC arm. Patients had RET fusion-positive disease that was previously treated with platinum chemotherapy. ORR was 64%, and 81% had a response to treatment lasting 6 months or longer. The drug was also evaluated in 39 patients with RET fusion-positive NSCLC that was untreated. ORR in that group was 84%, and 58% of patients had a response lasting at least 6 months.

There were 143 patients evaluated in the medullary thyroid cancer arm: 55 were previously treated with cabozantinib, vanddtanib, or both; as well as88 patients with advanced or metastatic RET-mutant disease who did not have prior treatment with these agents. The ORR for the previously treated patients was 69%. Seventy-six percent of patients who responded had responses that lasted 6 or more months. For the previously untreated patients, ORR was 73%, with 61% having responses lasting 6 or more months.

Nineteen patients were evaluated that had RET fusion-positive thyroid cancer who refractory to radioactive iodine-refractory and had another treatment. ORR for the previously-treated patients was 79% -- 87% of them had a response lasting 6 or more months. For those who did not have radioactive iodine treatment, there was a 100% ORR. Seventy-five percent of these patients had a response that lasted 6 or more months.

Serious adverse events (AEs) for selpercatinib were hepatoxicity, elevated blood pressure, QT prolongation, bleeding, and allergic reactions. If patients experience liver damage, the drug should be withheld, dose reduced, or permanently discontinued.

Common AEs were increased aspartate aminotransferase and alanine aminotransferase enzymes in the live, increased blood sugar, decreased white blood cell count, decreased aluminum in the blood, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphate, hypertension, fatigue, swelling, low blood platelet count, increased cholesterol, rash, constipation, and decreased sodium.

“The FDA is committed to reviewing treatments like Retevmo that are targeted to specific subsets of people with cancer,” Pazdur said.