{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T21:52:18Z","timestamp":1794433938208,"version":"4.9.1"},"reference-count":41,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb Co","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013733","name":"Ipsen Biopharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["annalsofoncology.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Annals of Oncology"],"published-print":{"date-parts":[[2024,4]]},"DOI":"10.1016\/j.annonc.2023.12.008","type":"journal-article","created":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T01:31:45Z","timestamp":1703467905000},"page":"381-391","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":66,"title":["Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040"],"prefix":"10.1016","volume":"35","author":[{"given":"A.B.","family":"El-Khoueiry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Trojan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Yau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Melero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.-Y.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.-P.","family":"Choo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.-K.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Chopra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Soleymani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Neely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tschaika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.H.","family":"Welling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Sangro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.annonc.2023.12.008_bib1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.annonc.2023.12.008_bib3","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.annonc.2023.12.008_bib4","doi-asserted-by":"crossref","DOI":"10.1056\/EVIDoa2100070","article-title":"Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","volume":"1","author":"Abou-Alfa","year":"2022","journal-title":"NEJM Evid"},{"key":"10.1016\/j.annonc.2023.12.008_bib5","unstructured":"Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae) for Hepatocellular carcinoma V.1.2023. \u00a9 National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed March 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org."},{"key":"10.1016\/j.annonc.2023.12.008_bib6","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2022.40.4_suppl.379","article-title":"Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA","volume":"40","author":"Abou-Alfa","year":"2022","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib7","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\u00a0Hepatol"},{"key":"10.1016\/j.annonc.2023.12.008_bib8","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.annonc.2023.12.008_bib9","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\u00a0Engl J Med"},{"key":"10.1016\/j.annonc.2023.12.008_bib10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S1470-2045(21)00604-5","article-title":"Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial","volume":"23","author":"Yau","year":"2022","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib11","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.1200\/JCO.2021.39.15_suppl.4074","article-title":"Pembrolizumab (pembro) monotherapy for previously untreated advanced hepatocellular carcinoma (HCC): phase 2 KEYNOTE-224 study","volume":"39","author":"Laethem","year":"2021","journal-title":"J\u00a0Clinl Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib12","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\u00a0Engl J Med"},{"key":"10.1016\/j.annonc.2023.12.008_bib13","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.annonc.2023.12.008_bib14","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 alpha-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.annonc.2023.12.008_bib15","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1016\/S0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.annonc.2023.12.008_bib16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1200\/JCO.2018.36.4_suppl.475","article-title":"Impact of antitumor activity on survival outcomes, and nonconventional benefit, with nivolumab (NIVO) in patients with advanced hepatocellular carcinoma (aHCC): subanalyses of CheckMate-040","volume":"36","author":"El-Khoueiry","year":"2018","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib17","doi-asserted-by":"crossref","first-page":"e1532","DOI":"10.1634\/theoncologist.2019-0591","article-title":"Nivolumab in advanced hepatocellular carcinoma: safety profile and select treatment-related adverse events from the CheckMate 040 study","volume":"25","author":"Julien","year":"2020","journal-title":"Oncologist"},{"key":"10.1016\/j.annonc.2023.12.008_bib18","series-title":"Hepatic safety and biomarker assessments in sorafenib-experienced patients with advanced hepatocellular carcinoma treated with nivolumab in the CheckMate-040 study","author":"Meyer","year":"2018"},{"key":"10.1016\/j.annonc.2023.12.008_bib19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1001\/jamaoncol.2020.6968","article-title":"Updating reports of phase 3 clinical trials for cancer","volume":"7","author":"Elimova","year":"2021","journal-title":"JAMA Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib20","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1158\/1538-7445.AM2019-2675","article-title":"Assessment of inflammation biomarkers in relation to clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma in CheckMate 040","volume":"79","author":"Melero","year":"2019","journal-title":"Cancer Res"},{"key":"10.1016\/j.annonc.2023.12.008_bib21","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.jhep.2019.05.014","article-title":"Nivolumab in advanced hepatocellular carcinoma: sorafenib-experienced Asian cohort analysis","volume":"71","author":"Yau","year":"2019","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.annonc.2023.12.008_bib22","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1097\/00000421-198212000-00014","article-title":"Toxicity and response criteria of the Eastern Cooperative Oncology Group","volume":"5","author":"Oken","year":"1982","journal-title":"Am J Clin Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib23","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.annonc.2023.12.008_bib24","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1055\/s-0030-1247132","article-title":"Modified RECIST (mRECIST) assessment for hepatocellular carcinoma","volume":"30","author":"Lencioni","year":"2010","journal-title":"Semin Liver Dis"},{"key":"10.1016\/j.annonc.2023.12.008_bib25","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.jhep.2020.07.026","article-title":"Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma","volume":"73","author":"Sangro","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.annonc.2023.12.008_bib26","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S1470-2045(16)30098-5","article-title":"Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1\/2 trial","volume":"17","author":"Antonia","year":"2016","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib27","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.annonc.2023.12.008_bib28","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","article-title":"Nivolumab versus everolimus in advanced renal-cell carcinoma","volume":"373","author":"Motzer","year":"2015","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.annonc.2023.12.008_bib29","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1016\/S1470-2045(16)30496-X","article-title":"Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1\/2 trial","volume":"17","author":"Sharma","year":"2016","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib30","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jhep.2021.04.047","article-title":"CheckMate 040 cohort 5: a phase I\/II study of nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh B cirrhosis","volume":"75","author":"Kudo","year":"2021","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.annonc.2023.12.008_bib31","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/S1470-2045(18)30351-6","article-title":"Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial","volume":"19","author":"Zhu","year":"2018","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1200\/JCO.19.01307","article-title":"Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial","volume":"38","author":"Finn","year":"2020","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1200\/JCO.2022.40.4_suppl.383","article-title":"Pembrolizumab plus best supportive care versus placebo plus best supportive care as second-line therapy in patients in Asia with advanced hepatocellular carcinoma (HCC): phase 3 KEYNOTE-394 study","volume":"40","author":"Qin","year":"2022","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib34","doi-asserted-by":"crossref","first-page":"669","DOI":"10.21037\/tcr-21-2334","article-title":"Serum alpha-fetoprotein as a predictive biomarker for tissue alpha-fetoprotein status and prognosis in patients with hepatocellular carcinoma","volume":"11","author":"Wei","year":"2022","journal-title":"Transl Cancer Res"},{"key":"10.1016\/j.annonc.2023.12.008_bib35","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.jhep.2017.06.026","article-title":"Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies","volume":"67","author":"Bruix","year":"2017","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.annonc.2023.12.008_bib36","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.86182","article-title":"PD-1(+) and Foxp3(+) T cell reduction correlates with survival of HCC patients after sorafenib therapy","volume":"1","author":"Kalathil","year":"2016","journal-title":"JCI Insight"},{"key":"10.1016\/j.annonc.2023.12.008_bib37","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/1477-7819-11-212","article-title":"Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy","volume":"11","author":"Ma","year":"2013","journal-title":"World J Surg Oncol"},{"key":"10.1016\/j.annonc.2023.12.008_bib38","doi-asserted-by":"crossref","first-page":"S451","DOI":"10.1016\/S0168-8278(15)30585-7","article-title":"Gideon: a retrospective analysis of prognostic factors for survival","volume":"62","author":"Bronowicki","year":"2015","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.annonc.2023.12.008_bib39","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/s41591-022-01868-2","article-title":"Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma","volume":"28","author":"Zhu","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.annonc.2023.12.008_bib40","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1158\/1538-7445.AM2022-2145","article-title":"Abstract 2145: Genomic and transcriptomic analyses related to the clinical efficacy of first-line nivolumab in advanced hepatocellular carcinoma from the phase 3 CheckMate 459 trial","volume":"82","author":"Neely","year":"2022","journal-title":"Cancer Res"},{"key":"10.1016\/j.annonc.2023.12.008_bib41","doi-asserted-by":"crossref","first-page":"5394","DOI":"10.1158\/1078-0432.CCR-16-2842","article-title":"Nivolumab exposure-response analyses of efficacy and safety in previously treated squamous or nonsquamous non-small cell lung cancer","volume":"23","author":"Feng","year":"2017","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.annonc.2023.12.008_bib42","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/psp4.12133","article-title":"Quantitative characterization of the exposure-response relationship for cancer immunotherapy: a case study of nivolumab in patients with advanced melanoma","volume":"6","author":"Wang","year":"2017","journal-title":"CPT Pharmacometrics Syst Pharmacol"}],"container-title":["Annals of Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923753423051153?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923753423051153?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T01:04:27Z","timestamp":1729127067000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0923753423051153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["S0923753423051153"],"URL":"https:\/\/doi.org\/10.1016\/j.annonc.2023.12.008","relation":{},"ISSN":["0923-7534"],"issn-type":[{"value":"0923-7534","type":"print"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040","name":"articletitle","label":"Article Title"},{"value":"Annals of Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.annonc.2023.12.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology.","name":"copyright","label":"Copyright"}]}}