{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:45:31Z","timestamp":1785908731616,"version":"3.56.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Phase III trials of first-line immunotherapy-based combinations for advanced hepatocellular carcinoma (HCC) have yielded heterogeneous results, and head-to-head comparisons remain scarce. We evaluated mechanism-based strategy classes and individual regimens using a dual-level Bayesian network meta-analysis to provide a structured interpretation of the current evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched the literature up to December 28, 2025, and identified 15 phase III randomised controlled trials. A dual-level Bayesian network meta-analysis was performed using separate models at the strategy level (PD-(L)1 plus VEGF monoclonal antibody (VEGF(Ab)), PD-(L)1 plus tyrosine kinase inhibitor (TKI), PD-(L)1 plus CTLA-4, and PD-(L)1 monotherapy) and the regimen level. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade \u22653 treatment-related adverse events (TRAEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifteen trials comprising 9,792 patients were included. At the strategy level, PD-(L)1 plus VEGF(Ab) showed the most favourable OS effect versus TKI monotherapy and the highest efficacy-oriented ranking, followed by PD-(L)1 plus CTLA-4 and PD-(L)1 plus TKI. PD-(L)1 plus TKI also improved PFS but was associated with a higher toxicity and discontinuation burden, whereas PD-(L)1 monotherapy showed the most favourable tolerability profile. At the regimen level, atezolizumab plus bevacizumab, sintilimab plus IBI305, camrelizumab plus rivoceranib, and STRIDE showed OS benefit versus sorafenib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this evidence network, PD-(L)1 plus VEGF(Ab) showed the most efficacy-oriented profile and was supported by relatively consistent regimen-level estimates. However, the clinical interpretation of strategy-level findings differed across classes: PD-(L)1 plus TKI required closer regimen-level assessment because of greater within-class variability and a less favourable toxicity profile, whereas PD-(L)1 plus CTLA-4 and PD-(L)1 monotherapy showed distinct benefit-risk patterns. This dual-level framework complements regimen-centric evidence by distinguishing strategy-level patterns from regimen-level findings and by supporting a structured interpretation of efficacy-toxicity trade-offs in first-line ICI-based therapy for advanced HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251273309<\/jats:ext-link>\n                      , identifier CRD420251273309.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1907830","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:53:50Z","timestamp":1785905630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A dual-level Bayesian network meta-analysis 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