Efficacy of triple therapy and exploration of factors influencing treatment benefit in unresectable hepatocellular carcinoma: a meta-analysis

Background This meta-analysis evaluated the efficacy of transarterial chemoembolization (TACE) combined with anti-vascular endothelial growth factor (VEGF)/tyrosine kinase inhibitors (TKIs) and programed cell death protein 1 (PD-1)/programed cell death protein ligand 1 (PD-L1) inhibitors in unresectable hepatocellular carcinoma (uHCC), as well as the relevant influencing factors. Methods Four databases were searched through August 2026 for studies comparing TACE plus anti-VEGF/TKIs and PD-1/PD-L1 inhibitors with other regimens in uHCC. Random-effects models were used to pool hazard ratios (HRs) with corresponding 95% confidence intervals (95%CIs). The outcome s of this study were progression-free survival (PFS) and overall survival (OS). Exploratory subgroup analyses were performed based on patient and tumor characteristics. Results A total of 31 studies comprising over 8,900 patients were included. The triple therapy group was associated with significantly improved PFS (HR = 0.49, 95%CI [0.43, 0.55], p<0.001) and OS (HR = 0.45, 95%CI [0.39, 0.53], p<0.001) compared with the control group. Exploratory subgroup analyses suggested that younger patients (<50–65 years old), those with an Eastern Cooperative Oncology Group performance status of 0, patients with hepatitis B virus infection, patients without portal vein tumor thrombus, extrahepatic metastasis, or vascular invasion, and those with up-to-seven criteria>7 (especially the largest tumor size>10 cm) might have a better survival with the triple regimen. Conclusion Triple therapy with TACE, anti-VEGF/TKIs, and PD-1/PD-L1 inhibitors was associated with significantly improved prognosis in uHCC.