A dual-level Bayesian network meta-analysis of first-line immunotherapy in advanced hepatocellular carcinoma: strategy-level and regimen-level evidence
Abstract
Background: 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.
Methods: 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 ≥3 treatment-related adverse events (TRAEs).
Results: 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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 9,792 participants or records.
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