Selpercatinib in the treatment of thyroid cancer.

Selpercatinib, a highly selective RET inhibitor, represents a major advancement for RET-driven thyroid cancers, including medullary thyroid cancer (MTC) and radioiodine-refractory differentiated thyroid cancer (DTC). Clinical trials, such as LIBRETTO-001 and LIBRETTO-531, demonstrate its superior efficacy, safety, and tolerability compared to the less specific multikinase inhibitors, with overall response rates exceeding 84% in treatment-naïve RET-mutant MTC and 95% in RET fusion-positive DTC. Real-world studies further confirm its long-term benefits in diverse populations. With approvals from the U.S. FDA and EMA, selpercatinib is recommended as a first-line therapy for advanced RET-mutant MTC and as a second-line option for RAIR DTC. This review explores the molecular underpinnings of thyroid cancer, highlights the therapeutic landscape, and delves into the clinical performance of selpercatinib.