FDA approves selpercatinib for medullary thyroid cancer with a RET mutation
Regulatory approval news: On May 29, 2024, the FDA granted accelerated approval to selpercatinib (Retevmo) for pediatric patients aged ≥2 years with advanced or metastatic medullary thyroid cancer (MTC) harboring a RET mutation detected by an FDA-approved test, who require systemic therapy. The FDA cited LIBRETTO-531, where selpercatinib improved progression-free survival versus cabozantinib or vandetanib in adults/adolescents with RET-mutant MTC. Common adverse reactions included hypertension, edema, dry mouth, fatigue, and diarrhea.
FDA action (regulatory approval)
Date: 2024-05-29
The FDA granted accelerated approval to selpercatinib (Retevmo; Eli Lilly and Company) for pediatric patients aged 2 years 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 previously received accelerated approval in 2020 for this indication in patients ≥12 years. (The FDA later reported traditional approval on September 27, 2024, for adults and pediatric patients ≥2 years.)
Supporting evidence
Efficacy was evaluated in LIBRETTO-531 (NCT04211337), a randomized, multicenter, open-label study in adults and adolescents with advanced/metastatic RET-mutant MTC. Patients were randomized 2:1 to selpercatinib 160 mg twice daily vs physician’s choice of cabozantinib 140 mg once daily or vandetanib 300 mg once daily, stratified by RET mutation (M918T vs other) and intended control therapy.
Primary endpoint was PFS (BIRC; RECIST v1.1): median PFS NR (95% CI: NE, NE) with selpercatinib vs 16.8 months (95% CI: 12.2–25.1) with cabozantinib/vandetanib (HR 0.280, 95% CI: 0.165–0.475; p<0.0001). Patient-reported analyses indicated less time with severe side-effect bother on selpercatinib.
Safety (selected)
Common adverse reactions (≥25%): hypertension, edema, dry mouth, fatigue, diarrhea. Common grade 3/4 lab abnormalities (≥5%): decreased lymphocytes/neutrophils/calcium; increased ALT/AST/ALP/creatinine.