Combination immunotherapy and targeted therapy regimens show favorable survival outcomes versus monotherapies in unresectable hepatocellular carcinoma.

Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide. Because many patients present with unresectable disease at diagnosis and are therefore not candidates for curative resection, systemic therapy has become the cornerstone of first-line treatment for unresectable hepatocellular carcinoma (uHCC). We used parametric survival models to assess the efficacy of immunotherapy and targeted therapy as first-line strategies for treating uHCC, based on an analysis of the evidence from phase III trials, including phase II–III trials from which randomized phase III cohort data could be extracted. A systematic literature search of PubMed, Embase, and the Cochrane Library was conducted to identify randomized controlled trials reporting overall survival (OS) and progression-free survival (PFS) as Kaplan–Meier curves (KM curves). Individual patient data (IPD) were reconstructed from the published curves using digitization methods, and a pooled analysis of parametric survival curves was performed within a Bayesian framework to estimate time-dependent hazard ratios (HRs) and survival probabilities. Fifteen randomized trials involving patients with uHCC were included in the main analysis, and an additional sensitivity analysis explored the potential influence of CheckMate-9DW. The log-normal model provided the best fit for both OS and PFS data. Time-dependent HR analyses indicated clear departures from the proportional hazards (PH) assumption, suggesting that treatment effects varied over time. Combination regimens generally demonstrated more favorable survival outcomes than monotherapies. Among all evaluated treatments, finotonlimab plus bevacizumab biosimilar consistently showed the highest predicted OS and PFS probabilities across multiple time points. Combination regimens generally showed more favorable survival outcomes than monotherapies in first-line uHCC. Parametric survival modeling suggested that treatment effects varied over time and provided additional insights beyond conventional approaches based on constant HRs. Among the evaluated regimens, finotonlimab plus bevacizumab biosimilar showed a highly favorable efficacy profile; however, long-term comparisons should be interpreted cautiously because they depend partly on extrapolated estimates.