LIBRETTO-531

LIBRETTO-531, trial NCT04211337 sponsored by Eli Lilly and reported in 2023, showed that a drug built specifically for the RET mutation beats the older multi-target tablets in untreated progressive RET-mutant medullary thyroid cancer, with far fewer side effects. It randomised 291 patients to selpercatinib or cabozantinib or vandetanib, met its primary progression-free survival endpoint with a large effect, improved treatment failure-free survival and roughly halved the rate of severe adverse events, the first randomised proof that RET-selective therapy should be first line. OnCo links it to thyroid cancer and multiple endocrine neoplasia syndromes, kinase inhibitors, RET as a target, selpercatinib, vandetanib, LIBRETTO-431 and Lori J. Wirth. Whether resistance to selective RET inhibition can be met by next-generation drugs is the open question.