On September 27, 2024, the Food and Drug Administration granted traditional approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy.
Selpercatinib 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.
Efficacy was evaluated in LIBRETTO-531 (NCT04211337), a randomized, multicenter, open-label study in adults and adolescents with advanced or metastatic RET-mutant MTC. Patients were randomized (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 randomized to the control arm (cabozantinib vs. vandetanib).
The main efficacy outcome measure was progression-free survival (PFS), as determined by a blinded independent review committee according to RECIST v1.1. Median PFS was not reached (NR) (95% CI: not evaluable [NE], 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-value <0.0001). The clinical benefit of selpercatinib was supported by a pre-specified 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 (ALT), decreased neutrophils, increased alkaline phosphatase (ALP), increased blood creatinine, decreased calcium, and increased aspartate aminotransferase (AST).
The recommended selpercatinib dose for pediatric patients 2 to less than 12 years of age is based on body surface area and is based on weight for patients 12 years of age and older. See the prescribing information for specific dosing information.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review, breakthrough designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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