FDA Approves Retevmo® for RET-Mutated Lung, Thyroid Cancers

The U.S. Food and Drug Administration approved Retevmo® (selpercatinib) for three types of RET-mutated cancer: adults with metastatic RET-fusion-positive non-small cell lung cancer (NSCLC); adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy; and adult and pediatric patients ≥12 years of age with advanced or metastatic RET-fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine, when appropriate.

The decision was based on results from the multicenter, open-label, multicohort LIBRETTO-001 trial that included patients with RET-mutated tumors, which were prospectively determined in local laboratories using either next-generation sequencing, polymerase chain reaction, or fluorescence in situ hybridization. Patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity.

Responses observed with selpercatinib

A total of 105 adults with RET-fusion-positive NSCLC who previously received platinum chemotherapy were evaluated. The overall response rate (ORR) was 64% (95% CI, 54-73), and 81% of those who responded had responses lasting six months or longer. Efficacy was also evaluated in 39 patients who never received systemic treatment. The ORR in this cohort was 85% (95% CI, 70-94), with 58% of these patients having responses lasting six months or longer.

Among patients with advanced or metastatic RET-mutant MTC, the ORR for the 55 patients previously treated with cabozantinib, vandetanib, or both was 69% (95% CI, 55-81), and 76% of those who responded had a response that lasted six months or longer. Efficacy was also evaluated in 88 patients who had not received cabozantinib and/or vandetanib; the ORR for these patients was 73% (95% CI, 62-82), 61% of whom had a response that lasted six months or longer.

Efficacy for RET-fusion-positive thyroid cancer was evaluated in 19 patients who were radioactive iodine-refractory and had received another prior systemic treatment, as well as in eight patients who were radioactive iodine-refractory and had not received any additional therapy. The ORR for previously treated patients was 79% (95% CI, 54-94), and 87% had responses lasting six months or longer. All eight patients who did not receive additional therapy experienced a reponse (95% CI, 63-100), 75% of whom had responses lasting six months or longer.

The most common adverse events associated with selpercatinib were increased aspartate aminotransferase, increased alanine aminotransferase, increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation.