{"entity":{"id":"libretto-531","kind":"trial","name":"LIBRETTO-531","aka":[],"tldr":"Showed that a drug built specifically for the RET mutation beats the older multi-target pills in medullary thyroid cancer, with far fewer side effects.","summary":"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.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04211337","url":"https://clinicaltrials.gov/study/NCT04211337"},{"label":"NEJM 2023","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2309719"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["ret"],"drugs":["selpercatinib"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":["libretto-431"],"people":["lori-wirth"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04211337","phase":"3","setting":"Untreated progressive RET-mutant medullary thyroid cancer: selpercatinib vs cabozantinib or vandetanib","sponsor":"Eli Lilly","result":"PFS HR 0.28; 12-month PFS 86.8% vs 65.7%.","started":"2020-02-11","startedType":"actual","yearReported":2023,"enrolled":291,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 12 months","primary":true,"unit":"%","arms":[{"name":"Selpercatinib","value":86.8},{"name":"Cabozantinib or vandetanib","value":65.7}],"hr":0.28,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2309719"}],"replication":"Consistent with single-arm LIBRETTO-001 and with pralsetinib (ARROW) activity in RET-mutant MTC."},"route":"/trials/libretto-531/","neighbours":{"cancer":[{"id":"multiple-endocrine-neoplasia","kind":"cancer","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/cancers/multiple-endocrine-neoplasia/"},{"id":"men2-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)","route":"/cancers/men2-syndrome/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"}],"drug":[{"id":"selpercatinib","kind":"drug","name":"Selpercatinib","route":"/drugs/selpercatinib/"},{"id":"vandetanib","kind":"drug","name":"Vandetanib","route":"/drugs/vandetanib/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"trial":[{"id":"libretto-431","kind":"trial","name":"LIBRETTO-431","route":"/trials/libretto-431/"}],"person":[{"id":"lori-wirth","kind":"person","name":"Lori J. Wirth","route":"/people/lori-wirth/"}],"paper":[{"id":"paper-libretto-531-nejm-2023","kind":"paper","name":"LIBRETTO-531: selpercatinib versus cabozantinib or vandetanib in advanced RET-mutant medullary thyroid cancer","route":"/key-papers/paper-libretto-531-nejm-2023/"}]}}