{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:35:42Z","timestamp":1786977342022,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lenvatinib (LEN) is the recommended first\u2010line therapy for unresectable hepatocellular carcinoma (uHCC), but resistance frequently develops, and limited data exist on second\u2010line treatments. This study evaluated the efficacy and safety with a focus on the sorafenib (SOR) or regorafenib (REG)\u2010 based monotherapy or combination therapy in patients with uHCC after failure of first\u2010line LEN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients with first\u2010line LEN failure between May 2018 and December 2023 were retrospectively collected. Based on second\u2010line regimens, 70 patients were divided into two groups: the TKI group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200921) and the TKI\u2010ICI group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200949). Overall survival (OS) and progression\u2010free survival (PFS) were analyzed by Kaplan\u2013Meier methods, and multivariate analysis was performed to identify prognostic factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the TKI\u2010ICI group, median PFS was 5.27\u2009months and median OS was 12.53\u2009months. In the TKI group, median PFS was 3.10\u2009months and median OS was 7.50\u2009months. The objective response rate (ORR) was 19.1% in the TKI group and 16.3% in the TKI\u2010ICI group. The disease control rate (DCR) was 85.7% in the TKI\u2010ICI group and 61.9% in the TKI group. In the TKI\u2010ICI cohort, multivariable Cox analysis revealed the high albumin to neutrophil ratio index (ANRI) was an independent predictor for PFS, while alpha\u2010fetoprotein &gt;\u2009400\u2009ng\/mL was the independent predictor for OS. Safety profiles in both cohorts showed manageable toxicity, with no treatment\u2010related deaths.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combination of TKI and ICI presents a promising second\u2010line treatment option after LEN failure, regardless of the specific second\u2010line TKI used.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70711","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T12:55:46Z","timestamp":1741438546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mono\u2010\n                    <scp>TKI<\/scp>\n                    and\n                    <scp>TKI<\/scp>\n                    Plus\n                    <scp>ICI<\/scp>\n                    in Unresectable Hepatocellular Carcinoma Progression on First\u2010Line Treatment of Lenvatinib: A Real\u2010World Study"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6805-4593","authenticated-orcid":false,"given":"Xue","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Cancer Center, Beijing Ditan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, Beijing Ditan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, Beijing Ditan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, Beijing Ditan Hospital Capital 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