FDA Approves Selpercatinib as First Therapy for Certain Patients With Lung, Thyroid Cancers

On May 8, 2020, the FDA approved selpercatinib (Retevmo; Loxo Oncology) capsules for the treatment of patients with non–small-cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and other types of thyroid cancers with tumors harboring a RET alteration. More specifically, selpercatinib is now indicated for the treatment of metastatic NSCLC in adults; advanced or metastatic MTC in patients aged ≥12 years who require systemic therapy; and advanced RET fusion–positive thyroid in patients aged ≥12 years who require systemic therapy with tumors that have stopped responding to, or is inappropriate 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 who previously had few,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence, in a press release by the organization, which approved selpercatinib under the Accelerated Approval pathway and granted the treatment Priority Review, Orphan Drug, and Breakthrough Therapy designations.

This approval was based on clinical trial data from 3 individual studies involving patients with each of the 3 indicated tumor types. These patients were given selpercatinib 160 mg twice daily until disease progression or unacceptable toxicity occurred, and the major efficacy end points were overall response rate (ORR) and duration of response (DOR).

Among 105 adults with RET fusion–positive NSCLC who previously received platinum chemotherapy, the ORR was 64%, with responses lasting ≥6 months in 81% of patients. For 39 patients with RET fusion–positive NSCLC who had never before received treatment, the ORR was 84%, with responses lasting ≥6 months in 58% of patients.

In the study of patients aged ≥12 years with advanced or metastatic RET-mutant MTC, 143 patients who previously did (n = 55) or did not (n = 88) receive cabozantinib, vandetanib, or both had ORRs of 69% and 73%, respectively. Among these respondents, 76% and 61% had responses lasting ≥6 months, respectively.

Among 19 patients aged ≥12 years with RET fusion-positive thyroid cancer refractory to radioactive iodine therapy who previously received another systemic treatment, the ORR was 79%, with responses lasting ≥6 months in 87% of patients. For 8 patients who had not received treatment other than radioactive iodine therapy, the ORR was 100%, with responses lasting ≥6 months in 75% of patients.

The most frequently reported side effects of selpercatinib were increased aspartate aminotransferase and alanine aminotransferase enzymes in the liver, increased blood sugar, leukopenia, hypoalbuminemia, hypocalcemia, 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.—Hina M. Porcelli

Source: US Food and Drug Administration. FDA Approves First Therapy for Patients with Lung and Thyroid Cancers with a Certain Genetic Mutation or Fusion. May 8, 2020. www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-lung-and-thyroid-cancers-certain-genetic-mutation-or-fusion. Accessed May 11, 2020.