{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:33:09Z","timestamp":1793151189515,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jhep-reports.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JHEP Reports"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.jhepr.2026.101893","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:31:56Z","timestamp":1778765516000},"page":"101893","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Second-line TKI after first-line immunotherapy-based treatment in advanced HCC: Reconstructed IPD meta-analysis"],"prefix":"10.1016","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-7817","authenticated-orcid":false,"given":"Erman","family":"Akkus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hobeika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8289-7741","authenticated-orcid":false,"given":"Julien","family":"Edeline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2287-0635","authenticated-orcid":false,"given":"Cl\u00e9mence","family":"Hollande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Allaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2554-1877","authenticated-orcid":false,"given":"Giuliana","family":"Amaddeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Regnault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lequoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Charles","family":"Nault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3919-4135","authenticated-orcid":false,"given":"Mohamed","family":"Bouattour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhepr.2026.101893_bib1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"10.1016\/j.jhepr.2026.101893_bib2","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.jhepr.2026.101893_bib3","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jhepr.2026.101893_bib4","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.jhepr.2026.101893_bib5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(16)32453-9","article-title":"Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"389","author":"Bruix","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.jhepr.2026.101893_bib6","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S1470-2045(18)30937-9","article-title":"Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased \u03b1-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"20","author":"Zhu","year":"2019","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib7","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMoa1717002","article-title":"Cabozantinib in patients with advanced and progressing hepatocellular carcinoma","volume":"379","author":"Abou-Alfa","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jhepr.2026.101893_bib8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.annonc.2025.02.006","article-title":"Hepatocellular carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"36","author":"Vogel","year":"2025","journal-title":"Ann Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib9","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.jhep.2021.11.030","article-title":"Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma","volume":"76","author":"Cheng","year":"2022","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhepr.2026.101893_bib10","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0140-6736(23)00961-3","article-title":"Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study","volume":"402","author":"Qin","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.jhepr.2026.101893_bib11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.annonc.2024.02.005","article-title":"Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","volume":"35","author":"Sangro","year":"2024","journal-title":"Ann Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib12","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1016\/S0140-6736(25)00403-9","article-title":"Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial","volume":"405","author":"Yau","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.jhepr.2026.101893_bib13","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"10.1016\/j.jhepr.2026.101893_bib14","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-076754","article-title":"ROB-ME: a tool for assessing risk of bias due to missing evidence in systematic reviews with meta-analysis","volume":"383","author":"Page","year":"2023","journal-title":"BMJ"},{"issue":"Suppl. 3","key":"10.1016\/j.jhepr.2026.101893_bib15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.7861\/fhj.10-3-s26","article-title":"Assessing the risk of bias in single-arm trials for systematic reviews: moving towards a more reliable evaluation of clinical evidence","volume":"10","author":"Alsinbili","year":"2023","journal-title":"Future Healthc J"},{"key":"10.1016\/j.jhepr.2026.101893_bib16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1471-2288-12-9","article-title":"Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves","volume":"12","author":"Guyot","year":"2012","journal-title":"BMC Med Res Methodol"},{"key":"10.1016\/j.jhepr.2026.101893_bib17","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/biomet\/81.3.515","article-title":"Proportional hazards tests and diagnostics based on weighted residuals","volume":"81","author":"Grambsch","year":"1994","journal-title":"Biometrika"},{"key":"10.1016\/j.jhepr.2026.101893_bib18","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1471-2288-13-152","article-title":"Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome","volume":"13","author":"Royston","year":"2013","journal-title":"BMC Med Res Methodol"},{"key":"10.1016\/j.jhepr.2026.101893_bib19","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1214\/aoms\/1177729756","article-title":"Transformations related to the angular and the square root","volume":"21","author":"Freeman","year":"1950","journal-title":"Ann Math Stat"},{"key":"10.1016\/j.jhepr.2026.101893_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J Stat Soft"},{"key":"10.1016\/j.jhepr.2026.101893_bib21","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1007\/s12072-022-10392-x","article-title":"Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment","volume":"16","author":"Chen","year":"2022","journal-title":"Hepatol Int"},{"key":"10.1016\/j.jhepr.2026.101893_bib22","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3350\/cmh.2023.0553","article-title":"Sorafenib vs. lenvatinib in advanced hepatocellular carcinoma after atezolizumab\/bevacizumab failure: a real-world study","volume":"30","author":"Chon","year":"2024","journal-title":"Clin Mol Hepatol"},{"key":"10.1016\/j.jhepr.2026.101893_bib23","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1016\/j.annonc.2025.05.166","article-title":"153P Evolution of second-line practices in the era of immunotherapy: real-life data from the French prospective CHIEF cohort","volume":"36","author":"Decraecker","year":"2025","journal-title":"Ann Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib24","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1159\/000531316","article-title":"Lenvatinib as second-line treatment after atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma: clinical results show importance of hepatic reserve function","volume":"101","author":"Hiraoka","year":"2023","journal-title":"Oncology"},{"key":"10.1016\/j.jhepr.2026.101893_bib25","first-page":"127","article-title":"Real-world study of systemic treatment after first-line atezolizumab plus bevacizumab for hepatocellular carcinoma in Asia-Pacific countries","volume":"14","author":"Lee","year":"2025","journal-title":"Liver Cancer"},{"key":"10.1016\/j.jhepr.2026.101893_bib26","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.annonc.2025.05.188","article-title":"175P Lenvatinib versus sorafenib as second-line treatment post atezolizumab plus bevacizumab for hepatocellular carcinoma: the LEVIATHAN study","volume":"36","author":"Lombardi","year":"2025","journal-title":"Ann Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib27","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.21873\/anticanres.16663","article-title":"Clinical outcomes with lenvatinib in patients previously treated with atezolizumab\/bevacizumab for advanced hepatocellular carcinoma","volume":"43","author":"Muto","year":"2023","journal-title":"Anticancer Res"},{"key":"10.1016\/j.jhepr.2026.101893_bib28","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1159\/000541018","article-title":"Lenvatinib versus sorafenib second-line therapy in patients with hepatocellular carcinoma progressed to atezolizumab plus bevacizumab: a retrospective real-world study","volume":"103","author":"Persano","year":"2025","journal-title":"Oncology"},{"key":"10.1016\/j.jhepr.2026.101893_bib29","doi-asserted-by":"crossref","DOI":"10.1177\/17588359231189425","article-title":"Beyond atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma: overall efficacy and safety of tyrosine kinase inhibitors in a real-world setting","volume":"15","author":"Falette-Puisieux","year":"2023","journal-title":"Ther Adv Med Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib30","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.1003426","article-title":"Lenvatinib as second-line treatment in patients with unresectable hepatocellular carcinoma: a retrospective analysis","volume":"12","author":"Qin","year":"2022","journal-title":"Front Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib31","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.3390\/cancers15225406","article-title":"Therapeutic efficacy and safety of lenvatinib after atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma","volume":"15","author":"Yano","year":"2023","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.jhepr.2026.101893_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2024.10.149","article-title":"LBA1 Multicenter phase II trial of lenvatinib in patients with advanced hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab (KCSG HB23-04)","volume":"35","author":"Yoo","year":"2024","journal-title":"Ann Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1159\/000512781","article-title":"Clinical outcomes with multikinase inhibitors after progression on first-line atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma: a multinational multicenter retrospective study","volume":"10","author":"Yoo","year":"2021","journal-title":"Liver Cancer"},{"key":"10.1016\/j.jhepr.2026.101893_bib34","doi-asserted-by":"crossref","first-page":"972","DOI":"10.3390\/cancers17060972","article-title":"Evaluating sorafenib (SORA-2) as second-line treatment for unresectable hepatocellular carcinoma: a European retrospective multicenter study","volume":"17","author":"M\u00f6hring","year":"2025","journal-title":"Cancers"},{"key":"10.1016\/j.jhepr.2026.101893_bib35","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1159\/000543666","article-title":"Multicenter phase 2 trial of second-line regorafenib in patients with unresectable hepatocellular carcinoma after progression on atezolizumab plus bevacizumab","volume":"14","author":"Cheon","year":"2025","journal-title":"Liver Cancer"},{"key":"10.1016\/j.jhepr.2026.101893_bib36","doi-asserted-by":"crossref","DOI":"10.1093\/oncolo\/oyaf252","article-title":"Real-world clinical outcomes of cabozantinib as a second-line treatment for advanced hepatocellular carcinoma: a retrospective US claims analysis","volume":"30","author":"Ahn","year":"2025","journal-title":"Oncologist"},{"key":"10.1016\/j.jhepr.2026.101893_bib37","article-title":"Lenvatinib vs. sorafenib as second-line treatment post atezolizumab plus bevacizumab for hepatocellular carcinoma: the LEVIATHAN study","volume":"7","author":"Lombardi","year":"2025","journal-title":"JHEP Rep"},{"key":"10.1016\/j.jhepr.2026.101893_bib38","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jhep.2025.08.020","article-title":"Multicenter single-arm phase II trial of lenvatinib in patients with advanced hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab","volume":"84","author":"Kim","year":"2026","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhepr.2026.101893_bib39","doi-asserted-by":"crossref","DOI":"10.1093\/annonc\/mdy432.034","article-title":"Lenvatinib acts as the salvage therapy for advanced hepatocellular carcinoma","volume":"29","author":"Hsieh","year":"2018","journal-title":"Ann Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib40","doi-asserted-by":"crossref","first-page":"101781","DOI":"10.1016\/j.aohep.2025.101781","article-title":"Treatment for hepatocellular carcinoma after immunotherapy","volume":"30","author":"Chan","year":"2025","journal-title":"Ann Hepatol"},{"key":"10.1016\/j.jhepr.2026.101893_bib41","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jhep.2024.03.033","article-title":"Multicentre phase II trial of cabozantinib in patients with hepatocellular carcinoma after immune checkpoint inhibitor treatment","volume":"81","author":"Chan","year":"2024","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhepr.2026.101893_bib42","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/S1470-2045(23)00469-2","article-title":"Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial","volume":"24","author":"Llovet","year":"2023","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.jhepr.2026.101893_bib43","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000520278","article-title":"First-Line immune checkpoint inhibitor-based sequential therapies for advanced hepatocellular carcinoma: rationale for future trials","volume":"11","author":"Cabibbo","year":"2022","journal-title":"Liver Cancer"},{"key":"10.1016\/j.jhepr.2026.101893_bib44","article-title":"Heterogeneity in adverse events related to atezolizumab-bevacizumab for hepatocellular carcinoma reported in real-world studies","volume":"6","author":"Campani","year":"2024","journal-title":"JHEP Rep"}],"container-title":["JHEP Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555926001643?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555926001643?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:40:46Z","timestamp":1793148046000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589555926001643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S2589555926001643"],"URL":"https:\/\/doi.org\/10.1016\/j.jhepr.2026.101893","relation":{},"ISSN":["2589-5559"],"issn-type":[{"value":"2589-5559","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Second-line TKI after first-line immunotherapy-based treatment in advanced HCC: Reconstructed IPD meta-analysis","name":"articletitle","label":"Article Title"},{"value":"JHEP Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhepr.2026.101893","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).","name":"copyright","label":"Copyright"}],"article-number":"101893"}}