A meta-analysis of immunotherapy combinations for first-line treatment in hepatocellular carcinoma: Efficacy and safety outcomes.

Abstract

577 Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Immune checkpoint inhibitors (ICPI), whether alone or in combination with other agents including tyrosine-kinase inhibitors (TKIs), has shown strong anti-tumor activity among patients with advanced HCC. We aim to perform a comparative analysis of ICPI-based combination treatment versus TKI monotherapy among advanced HCC patients. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a meta-analysis to evaluate the demographics, overall survival (OS), progression-free survival (PFS), and the frequency of all-grade adverse events (AEs) in patients with advanced HCC. Individual patient data (IPD) were reconstructed from Kaplan-Meier curves published across multiple clinical trials from 2018 to 2025. Results: We evaluated data from 4,429 patients, including 389 who received immune checkpoint inhibitors (ICPI) monotherapy, 878 treated with ICPI combined with bevacizumab, 728 treated with double ICPI therapy, 705 treated with ICPI plus TKI, and 1,729 who received tyrosine-kinase inhibitor (TKI) alone. The analysis revealed a median OS of 16.84 months (95% CI: 13.85-NA) in the ICPI monotherapy arm,19.09 months (95% CI: 17.10-21.27) in the ICPI+ bevacizumab arm, 19.58 months (95% CI: 17.56-23.32) in the duplet ICPI arm, 19.23 months (95% CI: 16.82-21.88) in the ICPI+ TKI group, and 15.30 months (95% CI: 13.96-16.27) in the TKI monotherapy arm (p<0.001). The median PFS values were 3.73 months (95% CI: 3.34-3.89), 5.75 months (95% CI: 5.55-6.74), 5.51 months (95% CI: 4.75-5.76), 6.17 months (95% CI: 5.58-7.07), and 5.42 months (95% CI: 4.76-5.51), respectively. Safety analysis outcomes revealed significantly higher rates of hypertension and platelet abnormalities in the ICPI+ TKI group, and increased diarrhea incidence in the TKI monotherapy and ICPI duplet groups. Conclusions: We found that duplet ICPI demonstrated improved OS and PFS compared to TKI and ICPI monotherapies and varying but tolerable safety profiles across regimens.