biostudies-literatureUnknown16Lin Y<h4>Background</h4>Immune checkpoint inhibitor (ICI) and targeted therapy (TT) combinations have emerged as promising first-line treatments for unresectable or advanced hepatocellular carcinoma (u/aHCC), leveraging synergistic anti-tumor effects. However, the comparative efficacy and safety of ICI-TT regimens <i>versus</i> sorafenib or lenvatinib (S/L) monotherapy require further elucidation across larger patient populations. This meta-analysis synthesizes data from phase 3 trials to evaluate the clinical benefits and risks of first-line ICI-TT combination therapy in u/aHCC.<h4>Methods</h4>We conducted systematic searches in PubMed and major oncology conference proceedings up to June 10, 2025. Eligible studies were randomized phase 3 trials comparing first-line ICI-TT <i>versus</i> S/L monFrontiers in immunology1667793https://www.ebi.ac.uk/biostudies/studies/S-EPMC12568680biostudies-literatureFirst-line immune checkpoint inhibitors plus targeted therapy versus sorafenib or lenvatinib monotherapy for unresectable or advanced hepatocellular carcinoma: a meta-analysis of phase 3 trials.PMC12568680Liao YShen JLin YLuo BfalseFirst-line immune checkpoint inhibitors plus targeted therapy versus sorafenib or lenvatinib monotherapy for unresectable or advanced hepatocellular carcinoma: a meta-analysis of phase 3 trials.<h4>Background</h4>Immune checkpoint inhibitor (ICI) and targeted therapy (TT) combinations have emerged as promising first-line treatments for unresectable or advanced hepatocellular carcinoma (u/aHCC), leveraging synergistic anti-tumor effects. However, the comparative efficacy and safety of ICI-TT regimens <i>versus</i> sorafenib or lenvatinib (S/L) monotherapy require further elucidation across larger patient populations. This meta-analysis synthesizes data from phase 3 trials to evaluate the clinical benefits and risks of first-line ICI-TT combination therapy in u/aHCC.<h4>Methods</h4>We conducted systematic searches in PubMed and major oncology conference proceedings up to June 10, 2025. Eligible studies were randomized phase 3 trials comparing first-line ICI-TT <i>versus</i> S/L mon2025-01-01T00:00:00Z20252026-06-05T09:26:25.263Z2026-05-15T03:12:48.385ZS-EPMC125686804116938510.3389/fimmu.2025.1667793