Selpercatinib Approved for RET Fusion-Positive Medullary Thyroid Cancer
Expert Perspectives · Lyn Brook · 2024-09-30
The FDA has granted approval to selpercatinib (Retevmo®, Eli Lilly and Company) for adult and pediatric patients two years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a rearranged during transfection (RET) mutation, as detected by an FDA-approved test, who require systemic therapy.
In 2020, selpercatinib received accelerated approval for this indication in patients 12 years of age and older. Earlier this year, selpercatinib received accelerated approval for this indication in pediatric patients two years of age and older.
Why it matters: “Medullary thyroid cancer is a neuroendocrine neoplasm with tumorogenesis driven mainly by alterations in the RET proto-oncogene,” wrote Julien Hadoux, MD, PhD, a Medical Oncology at Gustave Roussy in Villejuif, France, and colleagues, in their published results of the LIBRETTO-531 trial (NCT04211337), on which approval was based. “Selpurcatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer.”
What they studied: Efficacy was measured in the phase 3, open-label trial which enrolled adults and adolescents with advanced or metastatic RET-mutant MTC. Patients were randomized 2:1 to receive either 160 mg of selpercatinib twice daily or physician’s choice, which consisted of 140 mg cabozantinib once daily or 300 mg of vandetanib once daily. Stratification criteria was based on RET mutation (M918T or other) and intended treatment if randomized to the control arm.
The primary efficacy outcome measured was progression-free survival as determined by a blinded independent review committee according to RECIST v1.1.
What they found: The median progression-free survival was not reached in the selpercatinib arm compared with a median of 16.8 months in the physician’s choice arm. Selpercatinib was determined to have a clinical benefit due to a pre-specified analysis of patient-reported comparative side effect impact; patients who received selpercatinib experienced less time affected by severe side effects compared with those receiving cabozantinib or vandetanib.
Adverse events: The most common adverse events experienced by ≥25% of patients receiving selpercatinib were hypertension, edema, dry mouth, fatigue, and diarrhea. The most common Grade 3 or 4 laboratory abnormalities experienced by ≥5% were decreased lymphocytes, increased alanine aminotransferase (ALT), decreased neutrophils, increased alkaline phosphatase (ALP), increased blood creatinine, decreased calcium, and increased aspartate aminotransferase (AST).
Conclusion: “Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer,” concluded Dr. Hadoux and colleagues.
Instructions: The recommended dosage of selpercatinib for pediatric patients two to less than 12 years of age is based on body surface area. For patients 12 years of age and older, the recommended dosage is based on weight. Refer to the prescribing information for specific dosing information.