{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:50:09Z","timestamp":1791474609746,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 CA009679"],"award-info":[{"award-number":["T32 CA009679"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with decompensated cirrhosis are excluded or underrepresented in clinical trials of systemic therapies for hepatocellular carcinoma (HCC) and comparisons of available therapies are lacking. We aimed to compare overall survival for patients with HCC and Child\u2010Pugh B cirrhosis treated with nivolumab or sorafenib as first systemic treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective cohort study in patients with HCC and Child\u2010Pugh B cirrhosis treated at Veterans Affairs medical centers to compare overall survival, adverse events, and reason for discontinuation of therapy between patients treated with nivolumab or sorafenib as first systemic treatment. All statistical tests were 2\u2010sided.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of those meeting inclusion criteria, 431 patients were treated with sorafenib and 79 with nivolumab. Median OS was 4.0\u00a0months (95% CI 3.5\u20134.8) in the sorafenib cohort and 5.0\u00a0months (95% CI 3.3\u20136.8) in the nivolumab cohort. In the multivariable Cox proportional hazards model, nivolumab was associated with a significantly reduced hazard of death compared to sorafenib (HR 0.69; 95% CI 0.52\u20130.91; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.008). In a secondary analysis using propensity score methods, results did not reach statistical significance (HR 0.77; 95% CI 0.55\u20131.06; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.11). Treatment was discontinued due to toxicity in 12% of patients receiving nivolumab compared to 36% receiving sorafenib (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with HCC and Child\u2010Pugh B cirrhosis, nivolumab treatment may be associated with improved overall survival and improved tolerability compared to sorafenib and should be considered for the first systemic treatment in this population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4906","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T09:58:16Z","timestamp":1654163896000},"page":"189-199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and Child\u2010Pugh B cirrhosis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-8462","authenticated-orcid":false,"given":"William J.","family":"Chapin","sequence":"first","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Medicine, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2829-2167","authenticated-orcid":false,"given":"Wei\u2010Ting","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9157-5392","authenticated-orcid":false,"given":"Thomas B.","family":"Karasic","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Medicine, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3839-336X","authenticated-orcid":false,"given":"David E.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Corporal Michael J. Crescenz VA Medical Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.07.019"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840070408"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30207-1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00604-5"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708857"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.07.020"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.04.047"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.4_suppl.483"},{"key":"e_1_2_11_11_1","unstructured":"FDA 2019 FDA grants accelerated approval to nivolumab for HCC previously treated with sorafenib"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.07.010"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0801209"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.2148"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03362-0"},{"key":"e_1_2_11_16_1","volume-title":"Nature of veterans health administration facilities management (engineering) tasks and staffing","author":"National Academies of Sciences, Engineering, and Medicine; Division of Behavioral and Social Sciences and Education; Board on Human\u2010Systems Integration; Division on Engineering and Physical Sciences; Board on Infrastructure and the Constructed Environment; Committee on Facilities Staffing Requirements for Veterans Health Administration","year":"2019"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.09.019"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2016.05.040"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.03.038"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2015.01.012"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3921"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.8.1602"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.4_suppl.379"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-011-1616-x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27543"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071968"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32206"},{"key":"e_1_2_11_28_1","unstructured":"Research C for DEWithdrawn | Cancer accelerated approvals.FDA.2022. 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