{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:26:56Z","timestamp":1792193216187,"version":"4.4.0"},"reference-count":102,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cancertreatmentreviews.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Treatment Reviews"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.ctrv.2025.102955","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T12:59:00Z","timestamp":1746795540000},"page":"102955","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"C","title":["The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers"],"prefix":"10.1016","volume":"137","author":[{"given":"Giuseppe","family":"Cabibbo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-3615","authenticated-orcid":false,"given":"Lorenza","family":"Rimassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lamarca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Masi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Daniele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David James","family":"Pinato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Casadei-Gardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0005","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1159\/000456593","article-title":"Treating hepatobiliary cancer: the immunologic approach","volume":"35","author":"Duffy","year":"2017","journal-title":"Dig Dis"},{"issue":"9","key":"10.1016\/j.ctrv.2025.102955_b0010","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"3","key":"10.1016\/j.ctrv.2025.102955_b0015","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.ctrv.2025.102955_b0020","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejca.2021.11.023","article-title":"Global, regional and national burden of primary liver cancer by subtype","volume":"161","author":"Rumgay","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ctrv.2025.102955_b0025","unstructured":"International Agency for Research on Cancer. GLOBOCAN 2018. IARC https:\/\/gco.iarc.fr\/today\/online-analysis-map?v=2020&mode=population& mode_population=continents&population= 900&populations=900&key=asr&sex=0&cancer=11&type=0&statistic=5&prevalence=0&population_groupearth&color_palette=default&map_scale= quantile&map_nb_colors=5&continent=0&rotate= %255B10%252C0%255D (2020)."},{"key":"10.1016\/j.ctrv.2025.102955_b0030","article-title":"Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline update","author":"Rose","year":"2024","journal-title":"J Clin Oncol"},{"issue":"9","key":"10.1016\/j.ctrv.2025.102955_b0035","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-002794","article-title":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma","volume":"9","author":"Greten","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"2","key":"10.1016\/j.ctrv.2025.102955_b0040","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.annonc.2022.10.506","article-title":"Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Vogel","year":"2023","journal-title":"Ann Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0045","article-title":"on behalf of the ESMO Guidelines Committee. ESMO Clinical Practice Guideline interim update on the management of biliary tract cancer","author":"Vogel","year":"2024","journal-title":"ESMO Open"},{"issue":"1","key":"10.1016\/j.ctrv.2025.102955_b0050","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jhep.2012.02.022","article-title":"Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma","volume":"57","author":"Palmer","year":"2012","journal-title":"J Hepatol"},{"issue":"10","key":"10.1016\/j.ctrv.2025.102955_b0055","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/s41395-018-0207-4","article-title":"Body mass index, diabetes, and intrahepatic cholangiocarcinoma risk: the liver cancer pooling project and meta-analysis","volume":"113","author":"Petrick","year":"2018","journal-title":"Am J Gastroenterol"},{"issue":"10360","key":"10.1016\/j.ctrv.2025.102955_b0060","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular carcinoma","volume":"400","author":"Vogel","year":"2022","journal-title":"Lancet (London, England)"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0065","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/j.1478-3231.2009.01994.x","article-title":"Prognostic scores for hepatocellular carcinoma: none is the winner","volume":"29","author":"Camm\u00e0","year":"2009","journal-title":"Liver Int"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0070","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.dld.2022.01.122","article-title":"Italian Association for the Study of the Liver (AISF). Optimizing systemic therapy for advanced hepatocellular carcinoma: the key role of liver function","volume":"54","author":"Cabibbo","year":"2022","journal-title":"Dig Liver Dis"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0075","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1053\/j.seminoncol.2012.05.006","article-title":"Causes of and prevention strategies for hepatocellular carcinoma","volume":"39","author":"Cabibbo","year":"2012","journal-title":"Semin Oncol"},{"issue":"5","key":"10.1016\/j.ctrv.2025.102955_b0080","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.jhep.2021.01.046","article-title":"Antiviral therapy in the palliative setting of HCC (BCLC-B and -C)","volume":"74","author":"Reig","year":"2021","journal-title":"J Hepatol"},{"issue":"1","key":"10.1016\/j.ctrv.2025.102955_b0085","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jhep.2017.01.033","article-title":"Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma","volume":"67","author":"Cabibbo","year":"2017","journal-title":"J Hepatol"},{"issue":"2","key":"10.1016\/j.ctrv.2025.102955_b0090","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jhep.2019.03.027","article-title":"Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients","volume":"71","author":"Cabibbo","year":"2019","journal-title":"J Hepatol"},{"issue":"3","key":"10.1016\/j.ctrv.2025.102955_b0095","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1002\/hep.27729","article-title":"Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib","volume":"62","author":"Iavarone","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.ctrv.2025.102955_b0100","doi-asserted-by":"crossref","DOI":"10.1016\/S0168-8278(24)00519-1","article-title":"Hepatic decompensation is the major driver of mortality in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment","author":"Celsa","year":"2024","journal-title":"Hepatology"},{"issue":"16","key":"10.1016\/j.ctrv.2025.102955_b0105","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.3390\/cancers13164220","article-title":"Challenges for better diagnosis and management of pancreatic and biliary tract cancers focusing on blood biomarkers: a systematic review","volume":"13","author":"Tominaga","year":"2021","journal-title":"Cancers"},{"issue":"15","key":"10.1016\/j.ctrv.2025.102955_b0110","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.3748\/wjg.v28.i15.1508","article-title":"Novel approaches in search for biomarkers of cholangiocarcinoma","volume":"28","author":"Mocan","year":"2022","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.ctrv.2025.102955_b0115","doi-asserted-by":"crossref","unstructured":"EASL-ILCA clinical practice guidelines on the management of intrahepatic cholangiocarcinoma. J Hepatol. 2023;79(1):181-208. doi: 10.1016\/j.jhep.2023.03.010.","DOI":"10.1016\/j.jhep.2023.03.010"},{"issue":"12","key":"10.1016\/j.ctrv.2025.102955_b0120","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s40265-023-01907-3","article-title":"New opportunities to individualize frontline therapy in advanced stages of hepatocellular carcinoma","volume":"83","author":"Gordan","year":"2023","journal-title":"Drugs"},{"key":"10.1016\/j.ctrv.2025.102955_b0125","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer","volume":"362","author":"Valle","year":"2010","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ctrv.2025.102955_b0130","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2023.1128930","article-title":"Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy","volume":"13","author":"Casadei-Gardini","year":"2023","journal-title":"Front Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0135","doi-asserted-by":"crossref","DOI":"10.1056\/EVIDoa2200015","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer","volume":"1","author":"Oh","year":"2022","journal-title":"NEJM Evid"},{"issue":"8","key":"10.1016\/j.ctrv.2025.102955_b0140","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","article-title":"Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study","volume":"9","author":"Oh","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"10.1016\/j.ctrv.2025.102955_b0145","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","article-title":"Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Kelley","year":"2023","journal-title":"Lancet"},{"issue":"16 Suppl","key":"10.1016\/j.ctrv.2025.102955_b0150","doi-asserted-by":"crossref","first-page":"4093","DOI":"10.1200\/JCO.2024.42.16_suppl.4093","article-title":"Three-year follow-up data from KEYNOTE-966: Pembrolizumab (pembro) plus gemcitabine and cisplatin (gem\/cis) compared with gem\/cis alone for patients (pts) with advanced biliary tract cancer (BTC)","volume":"42","author":"Finn","year":"2024","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0155","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1002\/hep.26731","article-title":"Immunodominance and functional alterations of tumor-associated antigen-specific CD8+ T-cell responses in hepatocellular carcinoma","volume":"59","author":"Flecken","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.ctrv.2025.102955_b0160","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jhep.2005.12.027","article-title":"Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation","volume":"45","author":"Unitt","year":"2006","journal-title":"J Hepatol"},{"key":"10.1016\/j.ctrv.2025.102955_b0165","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ctrv.2019.05.004","article-title":"Management of adverse events associated with tyrosine kinase inhibitors: Improving outcomes for patients with hepatocellular carcinoma","volume":"77","author":"Rimassa","year":"2019","journal-title":"Cancer Treat Rev"},{"issue":"10088","key":"10.1016\/j.ctrv.2025.102955_b0170","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"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0175","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.annonc.2023.12.008","article-title":"Nivolumab in sorafenib-naive and sorafenib-experienced patients with advanced hepatocellular carcinoma: 5-year follow-up from CheckMate 040","volume":"35","author":"El-Khoueiry","year":"2024","journal-title":"Ann Oncol"},{"issue":"7","key":"10.1016\/j.ctrv.2025.102955_b0180","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"},{"issue":"1","key":"10.1016\/j.ctrv.2025.102955_b0185","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"},{"issue":"3","key":"10.1016\/j.ctrv.2025.102955_b0190","first-page":"193","article-title":"Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: A randomized, double-blind","volume":"38","author":"Finn","year":"2020","journal-title":"Phase III Trial J Clin Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0195","article-title":"Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","volume":"1(8):EVIDoa2100070","author":"Abou-Alfa","year":"2022","journal-title":"NEJM Evid"},{"issue":"12","key":"10.1016\/j.ctrv.2025.102955_b0200","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1001\/jamaoncol.2023.4003","article-title":"Tislelizumab vs sorafenib as first-line treatment for unresectable hepatocellular carcinoma: a phase 3 randomized clinical trial","volume":"9","author":"Qin","year":"2023","journal-title":"JAMA Oncol"},{"issue":"6","key":"10.1016\/j.ctrv.2025.102955_b0205","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.annonc.2024.03.005","article-title":"Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040","volume":"35","author":"Melero","year":"2024","journal-title":"Ann Oncol"},{"issue":"20","key":"10.1016\/j.ctrv.2025.102955_b0210","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 Engl J Med"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0215","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"},{"issue":"25","key":"10.1016\/j.ctrv.2025.102955_b0220","doi-asserted-by":"crossref","first-page":"00073","DOI":"10.1016\/j.annonc.2025.05.187","article-title":"ESMO guidelines committee. Hepatocellular carcinoma: ESMO clinical practice guideline for diagnosis, treatment and follow-up","volume":"S0923\u20137534","author":"Vogel","year":"2025","journal-title":"Ann Oncol"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0225","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.jhep.2021.07.004","article-title":"Systemic treatment of hepatocellular carcinoma: an EASL position paper","volume":"75","author":"Bruix","year":"2021","journal-title":"J Hepatol"},{"issue":"3","key":"10.1016\/j.ctrv.2025.102955_b0230","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1053\/j.gastro.2021.12.276","article-title":"AGA Clinical Practice Guideline on systemic therapy for hepatocellular carcinoma","volume":"162","author":"Su","year":"2022","journal-title":"Gastroenterology"},{"issue":"3","key":"10.1016\/j.ctrv.2025.102955_b0235","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.dld.2023.10.028","volume":"56","author":"Cabibbo","year":"2024","journal-title":"Dig Liver Dis"},{"issue":"5","key":"10.1016\/j.ctrv.2025.102955_b0240","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"},{"issue":"suppl_2","key":"10.1016\/j.ctrv.2025.102955_b0245","doi-asserted-by":"crossref","first-page":"S656","DOI":"10.1016\/j.annonc.2024.08.1007","article-title":"Five-year overall survival (OS) and OS by tumour response measures from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC)","volume":"35","author":"Rimassa","year":"2024","journal-title":"Ann Oncol"},{"issue":"6","key":"10.1016\/j.ctrv.2025.102955_b0250","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1097\/HEP.0000000000000466","article-title":"AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma","volume":"78","author":"Singal","year":"2023","journal-title":"Hepatology"},{"key":"10.1016\/j.ctrv.2025.102955_b0255","unstructured":"National Comprehensive Cancer Network. NCCN Guidelines version 3.2024: hepatocellular carcinoma. Accessed January 8th 2025. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/hcc.pdf."},{"key":"10.1016\/j.ctrv.2025.102955_b0260","doi-asserted-by":"crossref","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","author":"Yau","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.ctrv.2025.102955_b0265","doi-asserted-by":"crossref","unstructured":"T. Decaens, T. Yau, M. Kudo, B. Sangro, S. Qin, L. Da Fonseca, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC): Expanded analyses from CheckMate 9DW. Annals of Oncology 2024; 35 (suppl_2): S656-S673.doi: 10.1016\/j.annonc.2024.08.1025.","DOI":"10.1016\/j.annonc.2024.08.1025"},{"issue":"10408","key":"10.1016\/j.ctrv.2025.102955_b0270","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"},{"issue":"16 Suppl","key":"10.1016\/j.ctrv.2025.102955_b0275","article-title":"Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the phase 3 CARES-310 study","volume":"42","author":"Vogel","year":"2024","journal-title":"JCO"},{"issue":"12","key":"10.1016\/j.ctrv.2025.102955_b0280","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.ctrv.2025.102955_b0285","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S1470-2045(22)00326-6","article-title":"Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial","volume":"23","author":"Kelley","year":"2022","journal-title":"Lancet Oncol"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0290","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S2468-1253(23)00454-5","article-title":"Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): final results of a randomised phase 3 study","volume":"9","author":"Yau","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"10.1016\/j.ctrv.2025.102955_b0295","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/S1470-2045(21)00252-7","article-title":"Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study","volume":"22","author":"Ren","year":"2021","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0300","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000531744","article-title":"Balancing efficacy and tolerability of first-line systemic therapies for advanced hepatocellular carcinoma: a network meta-analysis","volume":"13","author":"Celsa","year":"2024","journal-title":"Liver Cancer"},{"issue":"5","key":"10.1016\/j.ctrv.2025.102955_b0305","article-title":"Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials","volume":"5","author":"Fulgenzi","year":"2023","journal-title":"JHEP Rep"},{"issue":"1","key":"10.1016\/j.ctrv.2025.102955_b0310","doi-asserted-by":"crossref","first-page":"69","DOI":"10.14218\/JCTH.2019.00050","article-title":"Liver transplantation beyond milan criteria","volume":"8","author":"Lingiah","year":"2020","journal-title":"J Clin Transl Hepatol"},{"issue":"2","key":"10.1016\/j.ctrv.2025.102955_b0315","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.dld.2023.10.029","volume":"56","author":"Cabibbo","year":"2024","journal-title":"Dig Liver Dis"},{"key":"10.1016\/j.ctrv.2025.102955_b0320","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.jhep.2021.11.018","article-title":"BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update","volume":"76","author":"Reig","year":"2022","journal-title":"J Hepatol"},{"issue":"7","key":"10.1016\/j.ctrv.2025.102955_b0325","doi-asserted-by":"crossref","first-page":"e312","DOI":"10.1016\/S1470-2045(23)00186-9","article-title":"Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept","volume":"24","author":"Vitale","year":"2023","journal-title":"Lancet Oncol"},{"issue":"3","key":"10.1016\/j.ctrv.2025.102955_b0330","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/liv.13242","article-title":"Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma","volume":"37","author":"Pecorelli","year":"2017","journal-title":"Liver Int"},{"issue":"suppl 1","key":"10.1016\/j.ctrv.2025.102955_b0335","first-page":"S1","article-title":"OS-114 Liver transplantation following hepatocellular carcinoma downstaging with atezolizumab\/bevacizumab: preliminary results of the prospective ImmunoXXL study","volume":"80","author":"Bhoori","year":"2024","journal-title":"J Hepatolgy"},{"issue":"12","key":"10.1016\/j.ctrv.2025.102955_b0340","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1111\/j.1600-6143.2008.02409.x","article-title":"Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria","volume":"8","author":"Ravaioli","year":"2008","journal-title":"Am J Transplant2"},{"issue":"7","key":"10.1016\/j.ctrv.2025.102955_b0345","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S1470-2045(20)30224-2","article-title":"Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b\/3 trial","volume":"21","author":"Mazzaferro","year":"2020","journal-title":"Lancet Oncol2"},{"key":"10.1016\/j.ctrv.2025.102955_b0350","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/hepr.13734","article-title":"Early experience of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma BCLC-B stage patients classified as beyond up to seven criteria-Multicenter analysis","volume":"52","author":"Hiraoka","year":"2022","journal-title":"Hepatol Res"},{"key":"10.1016\/j.ctrv.2025.102955_b0355","article-title":"EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization","volume":"42(suppl 3)","author":"Lencioni","year":"2024","journal-title":"JCO"},{"issue":"suppl 2","key":"10.1016\/j.ctrv.2025.102955_b0360","doi-asserted-by":"crossref","first-page":"S1229","DOI":"10.1016\/j.annonc.2024.08.2277","article-title":"Transarterial chemoembolization (TACE) with or without lenvatinib (len) + pembrolizumab (pembro) for intermediate-stage hepatocellular carcinoma (HCC): Phase III LEAP-012 study","volume":"35","author":"Llovet","year":"2024","journal-title":"Ann Oncol"},{"issue":"5","key":"10.1016\/j.ctrv.2025.102955_b0365","first-page":"399","article-title":"Atezolizumab plus Bevacizumab Followed by Curative Conversion (ABC Conversion) in Patients with Unresectable","volume":"11","author":"Kudo","year":"2022","journal-title":"TACE-Unsuitable Intermediate-Stage Hepatocellular Carcinoma Liver Cancer"},{"issue":"5","key":"10.1016\/j.ctrv.2025.102955_b0370","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1159\/000529996","article-title":"Albumin-bilirubin grade analyses of atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma: a post hoc analysis of the phase III IMbrave150 study","volume":"12","author":"Kudo","year":"2023","journal-title":"Liver Cancer"},{"issue":"7","key":"10.1016\/j.ctrv.2025.102955_b0375","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/S1470-2045(21)00151-0","article-title":"Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial","volume":"22","author":"Galle","year":"2021","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0380","doi-asserted-by":"crossref","DOI":"10.1177\/17588359221080298","article-title":"Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience","volume":"14","author":"de Castro","year":"2022","journal-title":"Ther Adv Med Oncol"},{"issue":"2","key":"10.1016\/j.ctrv.2025.102955_b0385","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11523-023-00953-x","article-title":"Real-world data for atezolizumab plus bevacizumab in unresectable Hepatocellular Carcinoma: how does adherence to the IMbrave150 trial inclusion criteria impact prognosis?","volume":"18","author":"Rimini","year":"2023","journal-title":"Target Oncol"},{"issue":"4","key":"10.1016\/j.ctrv.2025.102955_b0390","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/hep.32468","article-title":"Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study","volume":"76","author":"D'Alessio","year":"2022","journal-title":"Hepatology"},{"key":"10.1016\/j.ctrv.2025.102955_b0395","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ejca.2022.08.024","article-title":"Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study","volume":"175","author":"Fulgenzi","year":"2022","journal-title":"Eur J Cancer"},{"issue":"3","key":"10.1016\/j.ctrv.2025.102955_b0400","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1158\/1078-0432.CCR-24-2582","article-title":"Early hepatic decompensation identifies patients with hepatocellular carcinoma treated with Atezolizumab plus Bevacizumab or Sorafenib at highest risk of death","volume":"31","author":"Cabibbo","year":"2025","journal-title":"Clin Cancer Res"},{"issue":"2","key":"10.1016\/j.ctrv.2025.102955_b0405","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2024.104110","article-title":"Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial","volume":"10","author":"Piscaglia","year":"2025","journal-title":"ESMO Open"},{"key":"10.1016\/j.ctrv.2025.102955_b0410","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejca.2022.11.017","article-title":"Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population","volume":"180","author":"Casadei-Gardini","year":"2023","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ctrv.2025.102955_b0415","unstructured":"Abou-Alfa G, Chan S, Sangro B, Lau G, Kudo M, Breder V, et al. Subsequent anticancer therapy analysis of the Phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Oral presentation at the EASL Liver Cancer Summit, Paris, 20-22 February 2025."},{"issue":"Suppl 9","key":"10.1016\/j.ctrv.2025.102955_b0420","doi-asserted-by":"crossref","first-page":"S1465","DOI":"10.1016\/j.annonc.2022.10.119","article-title":"Impact of viral aetiology in the phase III HIMALAYA study of tremelimumab (T) plus durvalumab (D) in unresectable hepatocellular carcinoma (uHCC)","volume":"33","author":"Chan","year":"2022","journal-title":"Annals Oncol"},{"issue":"suppl_1","key":"10.1016\/j.ctrv.2025.102955_b0425","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1016\/j.annonc.2024.05.176","article-title":"167P - Non-viral aetiology subgroup of the phase III HIMALAYA study of tremelimumab (T) plus durvalumab (D) in unresectable hepatocellular carcinoma (uHCC)","volume":"35","author":"Reig Monzon","year":"2024","journal-title":"Ann Oncol"},{"issue":"suppl_1","key":"10.1016\/j.ctrv.2025.102955_b0430","first-page":"S75","article-title":"169P - Outcomes by comorbidities (CMs) with tremelimumab (T) and durvalumab (D) in the phase III HIMALAYA study in unresectable hepatocellular carcinoma (uHCC)","volume":"35","author":"Rimassa","year":"2024","journal-title":"Ann Oncol"},{"issue":"4 Suppl","key":"10.1016\/j.ctrv.2025.102955_b0435","article-title":"Outcomes of durvalumab (D) with or without tremelimumab (T) in routine clinical practice according to HIMALAYA trial eligibility: Preliminary results of the international DT-real study","volume":"43","author":"Celsa","year":"2025","journal-title":"JCO"},{"issue":"24","key":"10.1016\/j.ctrv.2025.102955_b0440","first-page":"00095","article-title":"Navigating the landscape of liver cancer management: Study designs in clinical trials and clinical practice","volume":"S0168\u20138278","author":"Cabibbo","year":"2024","journal-title":"J Hepatol"},{"key":"10.1016\/j.ctrv.2025.102955_b0445","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/S0140-6736(23)01796-8","article-title":"Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial","volume":"402","author":"Qin","year":"2023","journal-title":"Lancet"},{"issue":"suppl_2","key":"10.1016\/j.ctrv.2025.102955_b0450","first-page":"1","article-title":"Updated efficacy and safety data from IMbrave050: Phase III study of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients (pts) with resected or ablated high-risk hepatocellular carcinoma (HCC)","volume":"35","author":"Yopp","year":"2024","journal-title":"Ann Oncol"},{"issue":"5","key":"10.1016\/j.ctrv.2025.102955_b0455","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S1470-2045(24)00082-2","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"25","author":"Burris","year":"2024","journal-title":"Lancet Oncol"},{"issue":"8","key":"10.1016\/j.ctrv.2025.102955_b0460","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1111\/liv.15641","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data","volume":"43","author":"Rimini","year":"2023","journal-title":"Liver Int"},{"issue":"2","key":"10.1016\/j.ctrv.2025.102955_b0465","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11523-024-01044-1","article-title":"Durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer: an exploratory analysis of real-world data","volume":"19","author":"Olkus","year":"2024","journal-title":"Target Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0470","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1200\/JCO.2023.41.16_suppl.4003","article-title":"Health-related quality of life (HRQoL) in the phase 3 KEYNOTE-966 study of pembrolizumab (pembro) plus gemcitabine and cisplatin (gem\/cis) versus placebo plus gem\/cis for advanced biliary tract cancer (BTC)","volume":"41","author":"Yoo","year":"2023","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0475","article-title":"Atezolizumab plus chemotherapy with or without bevacizumab in advanced biliary tract cancer: clinical and biomarker data from the randomized phase II IMbrave151 trial","volume":"Oct 18","author":"Macarulla","year":"2024","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ctrv.2025.102955_b0480","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"},{"issue":"1","key":"10.1016\/j.ctrv.2025.102955_b0485","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":"2021","journal-title":"Liver Cancer"},{"issue":"2","key":"10.1016\/j.ctrv.2025.102955_b0490","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-001945","article-title":"Ipilimumab and nivolumab\/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors","volume":"9","author":"Wong","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"1","key":"10.1016\/j.ctrv.2025.102955_b0495","article-title":"Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma","volume":"5","author":"Scheiner","year":"2023","journal-title":"J Hep Reports"},{"issue":"4 suppl","key":"10.1016\/j.ctrv.2025.102955_b0500","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1200\/JCO.2022.40.4_suppl.433","article-title":"Regorafenib in patients with unresectable hepatocellular carcinoma (uHCC) in routine clinical practice: exploratory analysis of overall survival (OS) in the prospective, observational REFINE study","volume":"40","author":"Finn","year":"2022","journal-title":"J Clin Oncol"},{"issue":"24","key":"10.1016\/j.ctrv.2025.102955_b0505","first-page":"00216","article-title":"Multicentre phase II trial of cabozantinib in patients with hepatocellular carcinoma after immune checkpoint inhibitor treatment","volume":"S0168\u20138278","author":"Chan","year":"2024","journal-title":"J Hepatol"},{"issue":"16 Suppl","key":"10.1016\/j.ctrv.2025.102955_b0510","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1200\/JCO.2023.41.16_suppl.4004","article-title":"Outcomes by occurrence of immune-mediated adverse events (imAEs) with tremelimumab (T) plus durvalumab (D) in the phase 3 HIMALAYA study in unresectable hepatocellular carcinoma (uHCC)","volume":"41","author":"Lau","year":"2023","journal-title":"J Clin Oncol"}],"container-title":["Cancer Treatment Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0305737225000775?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0305737225000775?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T21:26:59Z","timestamp":1762291619000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0305737225000775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":102,"alternative-id":["S0305737225000775"],"URL":"https:\/\/doi.org\/10.1016\/j.ctrv.2025.102955","relation":{},"ISSN":["0305-7372"],"issn-type":[{"value":"0305-7372","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers","name":"articletitle","label":"Article Title"},{"value":"Cancer Treatment Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ctrv.2025.102955","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"102955"}}