Multinational phase 3 trial of first-line selpercatinib versus cabozantinib or vandetanib for advanced RET-mutant medullary thyroid cancer

Selpercatinib is a highly selective RET inihibitor. The multinational phase 3 LIBRETTO-531 trial compared first-line selpercatinib versus physician’s choice of cabozatinib or vandetanib for RET-mutant medullary thyroid cancer. At median follow-up 12 months, the median progression-free survival (primary end point) was not reached in the selpercatinib group and was 16.8 months in the control group (HR 0.28; p<0.001). Progression-free survival rate at 12 months was 86.8% in the selpercatinib group and 65.7% in the control group. Median treatment-free survival was not reached with selpercatinib and was 13.9 monhts with control (HR 0.25; p<0.001). Treatment-free survival rate at 12 monhts was 86.2% with selpercatinib and 62.1% with control. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group and 77.3% in the control group, and to discontinuation in 4.7% and 26.8%, respectively. The authors conclude that selpercatinib resulted in superior progression-free and treatment-free survival as compared with cabozatinib or vandetanib in patients with RET-mutant medullary thyroid cancer.