Integrating multiple outcomes of first-line immunotherapy-based regimens for advanced hepatocellular carcinoma: A network meta-analysis of phase III trials

Background Immunotherapy-based regimens are standard first-line treatments for advanced hepatocellular carcinoma (HCC), yet integrated comparisons across efficacy, safety, and quality-of-life (QoL) outcomes remain limited. We performed a network meta-analysis (NMA) to identify the optimal treatment strategy. Methods A literature search was conducted in PubMed, Embase, Cochrane Library, and Scopus to identify phase III randomized controlled trials (RCTs) evaluating immune checkpoint inhibitor (ICI)-based therapies. A Bayesian network meta-analysis was conducted to compare overall survival (OS), progression-free survival (PFS), tumor response, safety and QoL, with treatment rankings estimated using surface under the cumulative ranking curve (SUCRA) values. A subgroup analysis was conducted. A multi-criteria decision making approach, entropy-weighted Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) model was conducted to integrate efficacy, safety, and health-related QoL outcomes Results Twelve RCTs involving 7908 patients met inclusion criteria. Sintilimab plus IBI305 showed the highest probability of being the most effective treatment for overall survival with highest SUCRA scores (0.91). Finotonlimab plus bevacizumab was most likely to improve overall survival in younger patients (0.95) and those with HBV-related HCC (0.84), as well as PFS in the overall population (0.86). When integrating efficacy, safety, and health-related QoL outcomes, finotonlimab plus bevacizumab and atezolizumab plus bevacizumab demonstrated superior overall performance compared with all other regimens. Conclusions Bevacizumab-based immunotherapy combinations (finotonlimab plus bevacizumab and atezolizumab plus bevacizumab) provide a favorable benefit-risk balance in advanced HCC. The robust performance of finotonlimab plus bevacizumab highlights its translational potential. Composite points such as Topsis may facilitate integrated multiple outcomes. © 2026 Elsevier B.V.