Comparative efficacy and safety of first-line treatments for advanced hepatocellular carcinoma: a Bayesian network meta-analysis

Background The therapeutic landscape of advanced hepatocellular carcinoma (HCC) has expanded beyond sorafenib, with multiple combination regimens now demonstrating improved outcomes. However, the absence of direct head-to-head comparisons complicates treatment selection in clinical practice. Methods We performed a Bayesian network meta-analysis of phase III randomized controlled trials to compare the efficacy and safety of first-line treatments for patients with advanced HCC. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 adverse events were assessed. Treatment rankings were estimated using surface under the cumulative ranking curve values. Results Sixteen trials comprising 8, 753 patients were included. Hepatic arterial infusion chemotherapy (HAIC)-based regimens, particularly sorafenib plus HAIC and HAIC_FO, achieved the highest rankings for both PFS and OS. Several immunotherapy-based combinations also demonstrated significant survival benefits across multiple clinical subgroups without a corresponding increase in severe adverse events. Subgroup analyses suggested consistent benefits of selected regimens across age, sex, macrovascular invasion, extrahepatic spread, and ECOG performance status. Conclusions HAIC-based strategies and selected immunotherapy combinations appear to provide superior survival outcomes as first-line treatment for advanced HCC. Given limitations related to comparator selection and evolving evidence, future head-to-head randomized trials and updated network analyses are warranted to refine optimal treatment strategies. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251124082.