On September 27, 2024, the U.S. Food and Drug Administration granted traditional approval to selpercatinib (Retevmo) for adult and pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer with a RET mutation, as detected by an FDA-approved test, who require systemic therapy.
Selpercatinib previously received accelerated approval for this indication for patients 12 years of age and older in 2020. On May 29, 2024, the FDA granted accelerated approval for this indication to pediatric patients 2 years of age and older.
LIBRETTO-531
Efficacy was evaluated in LIBRETTO-531 (ClinicalTrials.gov identifier NCT04211337), a randomized, multicenter, open-label study in adults and adolescents with advanced or metastatic RET-mutant medullary thyroid cancer. Patients were randomly assigned (2:1) to receive either selpercatinib (160 mg twice daily) or physicians’ choice of cabozantinib (140 mg once daily) or vandetanib (300 mg once daily). Patients were stratified based on RET mutation (M918T vs other) and intended treatment if randomly assigned to the control arm (cabozantinib vs vandetanib).
The main efficacy outcome measure was progression-free survival, as determined by a blinded independent review committee according to Response Evaluation Criteria in Solid Tumors version 1.1. Median progression-free survival was not reached (95% confidence interval [CI] = not evaluable [NE] to NE) in the selpercatinib arm and 16.8 months (95% CI = 12.2–25.1) in the cabozantinib/vandetanib arm (hazard ratio = 0.280, 95% CI = 0.165–0.475; P < .0001). The clinical benefit of selpercatinib was supported by a prespecified analysis of patient-reported comparative side-effect impact; patients in the selpercatinib arm reported less time with severe side-effect bother than those receiving cabozantinib or vandetanib.
The most common adverse reactions (≥ 25%) were hypertension, edema, dry mouth, fatigue, and diarrhea. The most common grade 3 or 4 laboratory abnormalities (≥ 5%) were decreased lymphocytes, increased alanine aminotransferase, decreased neutrophils, increased alkaline phosphatase, increased blood creatinine, decreased calcium, and increased aspartate aminotransferase.
The recommended selpercatinib dose for pediatric patients aged 2 years to less than 12 years of age is based on body surface area and is based on weight for patients aged 12 years and older. See the prescribing information for specific dosing information.
