{"entity":{"id":"paper-libretto-431-nejm-2023","kind":"paper","name":"LIBRETTO-431: first-line selpercatinib versus chemotherapy with or without pembrolizumab in RET fusion-positive lung cancer","aka":[],"tldr":"Given as first treatment, selpercatinib more than doubled the time to progression compared with platinum-pemetrexed chemotherapy plus pembrolizumab in RET fusion-positive lung cancer, and protected against brain metastases.","summary":"Phase 3 trial of 261 patients with untreated advanced RET fusion-positive non-squamous non-small-cell lung cancer randomised to selpercatinib or platinum-pemetrexed with or without pembrolizumab.\n\nMedian progression-free survival was 24.8 versus 11.2 months (hazard ratio 0.46) in the intention-to-exclude-pembrolizumab population, response 84 versus 65 percent, and the cumulative incidence of central nervous system progression was lower with selpercatinib.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2309457"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870973/"}],"tags":[],"related":[],"cancers":["ret-fusion-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","selpercatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["libretto-431"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2309457","pmid":"37870973","authors":"Zhou C, Solomon B, Loong HH, et al.","paperType":"rct","findings":["Median progression-free survival 24.8 vs 11.2 months; hazard ratio 0.46.","Objective response 84 percent vs 65 percent."],"whatItMeans":"Selpercatinib is the established first-line treatment for RET fusion-positive lung cancer, and the trial adds to evidence that targeted therapy should precede chemo-immunotherapy in driver-positive disease.","caveats":["Open-label; overall survival immature.","Crossover to selpercatinib at progression was permitted."],"changedPractice":true,"participants":261},"route":"/key-papers/paper-libretto-431-nejm-2023/","neighbours":{"cancer":[{"id":"ret-fusion-nsclc","kind":"cancer","name":"RET fusion-positive non-small-cell lung cancer","route":"/cancers/ret-fusion-nsclc/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"selpercatinib","kind":"drug","name":"Selpercatinib","route":"/drugs/selpercatinib/"}],"trial":[{"id":"libretto-431","kind":"trial","name":"LIBRETTO-431","route":"/trials/libretto-431/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}