{"entity":{"id":"paper-leap-012-lancet-2025","kind":"paper","name":"LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma","aka":[],"tldr":"Adding lenvatinib and pembrolizumab to chemoembolisation delayed progression in intermediate-stage liver cancer, the second trial to show that systemic therapy improves on embolisation alone, at the cost of more side effects.","summary":"Phase 3 placebo-controlled trial of 480 patients with unresectable, non-metastatic hepatocellular carcinoma suitable for chemoembolisation randomised to transarterial chemoembolisation with lenvatinib plus pembrolizumab or with dual placebo.\n\nMedian progression-free survival was 14.6 versus 10.0 months (hazard ratio 0.66), with an early trend in overall survival (hazard ratio 0.80, not significant) and grade 3 to 4 treatment-related adverse events of 71 versus 32 percent.","asOf":"2026-09-17","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(24)02575-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39798578/"}],"tags":[],"related":[],"cancers":["hcc-intermediate"],"sections":[],"technologies":[],"targets":[],"drugs":["lenvatinib","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["leap-012"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(24)02575-3","pmid":"39798578","authors":"Kudo M, Ren Z, Guo Y, et al.","paperType":"rct","findings":["Median progression-free survival 14.6 vs 10.0 months; hazard ratio 0.66.","Grade 3 to 4 treatment-related adverse events 71 percent vs 32 percent."],"whatItMeans":"Lenvatinib-pembrolizumab with chemoembolisation is an emerging option for intermediate-stage disease, balanced against substantial toxicity.","caveats":["Overall survival not yet significant.","High toxicity may limit uptake."],"changedPractice":true,"participants":480},"route":"/key-papers/paper-leap-012-lancet-2025/","neighbours":{"cancer":[{"id":"hcc-intermediate","kind":"cancer","name":"Intermediate hepatocellular carcinoma (BCLC B)","route":"/cancers/hcc-intermediate/"}],"drug":[{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"trial":[{"id":"leap-012","kind":"trial","name":"LEAP-012","route":"/trials/leap-012/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}