On September 27, 2024, the U.S. Food and Drug Administration (FDA) granted traditional approval to selpercatinib (Retevmo®) for adult and pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer (MTC) with an RET variant, as detected by an FDA-approved test, who require systemic therapy.
Selpercatinib received accelerated approval for the indication for patients aged 12 and older in 2020. On May 29, 2024, the FDA granted accelerated approval for this indication to pediatric patients aged 2 and older.
Efficacy was evaluated in LIBRETTO-531 (NCT04211337), a randomized, multicenter, open-label study in adults and adolescents with advanced or metastatic RET-variant 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 variant (M918T or other) and intended treatment if randomized to the control arm (cabozantinib or 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 (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 (HR = 0.280 [95% CI = 0.165, 0.475]; p < 0.0001). The clinical benefit of selpercatinib was supported by a prespecified analysis of patient-reported comparative side effect impact; patients in the selpercatinib arm reported that severe side effects bothered them for less time than those receiving cabozantinib or vandetanib.
The most common adverse reactions reported in at least 25% of patients receiving selpercatinib were hypertension, edema, dry mouth, fatigue, and diarrhea. The most common grade 3 or 4 laboratory abnormalities reported in less than 5% of patients 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 is based on body surface area for pediatric patients aged 2–12 and is based on weight for patients aged 12 or older. See the prescribing information on Drugs@FDA for specific dosing information.
The applicant used the Assessment Aid to facilitate the FDA’s review. The FDA granted the application priority review, breakthrough designation, and orphan drug designation. FDA’s expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.