Evaluating the efficacy and safety of immunotherapy combinations as first-line treatment for hepatocellular carcinoma: A meta-analysis.

575 Background: Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths globally, with limited therapeutic options for patients in advanced stages. Immunotherapy, particularly in combination with other agents, has recently emerged as a promising first-line option. We aim to assess the efficacy and safety of various immunotherapy-based combination regimens in this setting. Methods: We extracted individual patient data (IPD) using Kaplan-Meier curves of published clinical trials from 2018 to 2025. A meta-analysis was conducted to assess the overall survival (OS), progression-free survival (PFS), and all grade adverse events (AEs) among study populations. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: We analyzed data from 3,335 patients, including 878 who received immune checkpoint inhibitors (ICPI) combined with bevacizumab, 728 treated with dual ICPI therapy, and 1,729 who received tyrosine-kinase inhibitor (TKI) alone. The analysis revealed a median OS of 19.09 months (95% CI: 17.09-21.27) in the ICPI+ bevacizumab arm, 19.58 months (95% CI: 17.55-23.32) in the dual ICPI arm, and 15.29 months (95% CI: 13.96-16.27) in the TKI monotherapy arm (p<0.001). The median PFS values were 5.76 months (95% CI: 5.55-6.74), 5.51 months (95% CI: 4.75-5.76), and 5.43 months (95% CI: 4.77-5.52), respectively. Toxicity profile analysis showed an increased incidence of diarrhea among patients who received TKI monotherapy (3.50%) and dual ICPI (2.49%), p=0.0027. Other AEs included platelet abnormalities, especially among the ICPI+ bevacizumab group (5.45%, p=0.0075), and body rash. Conclusions: We found that ICPI combinations, particularly dual ICPI, offer improved OS compared to other options among patients with advanced HCC, with comparable PFS. Although some AEs such as diarrhea and platelet abnormalities varied among arms, overall toxicity remains manageable.