Comparative efficacy and safety of immune checkpoint inhibitors combined with antiangiogenic agents for unresectable hepatocellular carcinoma in patients with Child-Pugh A versus B cirrhosis: a single-center, retrospective study

Background Immune checkpoint inhibitors (ICIs) combined with antiangiogenic agents (AAs) have been recommended as the first-line systemic treatment for unresectable hepatocellular carcinoma (uHCC). However, most Phase III clinical trials have excluded patients with Child-Pugh B (CP B) cirrhosis. This study aimed to evaluate the efficacy and safety of ICIs combined with AAs in uHCC patients with CP B cirrhosis and compare the outcomes with those in patients with Child-Pugh A (CP A) cirrhosis. Methods The uHCC patients who received ICIs plus AAs between September 2020 and November 2024 at Beijing You 'an Hospital were retrospectively analyzed. Tumor response and adverse events (AEs) were compared between the patients with CP A and CP B cirrhosis to assess the efficacy and safety of the treatment. Results A total of 94 patients were included in the study, including 63 patients with CP A cirrhosis and 31 with CP B cirrhosis. For the entire cohort, the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS) and median overall survival (mOS) were 44.7%, 72.3%, 6.3 months, and 28.3 months. The four indicators mentioned above were 50.8% vs 32.3% ( P  = 0.089), 76.2% vs 64.5% ( P  = 0.234), 6.6 months vs 5.8 months ( P  = 0.524) and 39.2 months vs 15.9 months ( P  = 0.035) in the CP A group and CP B group respectively, with only mOS showing a statistically significant difference between the two groups. The Barcelona Clinic Liver Cancer (BCLC) stage C/D was identified as an independent predictor of poorer OS. A total of 97.9% of patients experienced at least one AE of any grade, with 34.0% experiencing grade ≥ 3 AEs. The incidence and severity of AEs were similar between the patients with CP A and CP B cirrhosis. Additionally, Child-Pugh score improved in 32.3% of patients with CP B cirrhosis after systemic treatment. Conclusion The combination of ICIs and AAs showed favorable clinical benefits, safety and tolerability in uHCC patients with CP B cirrhosis, with some patients experiencing improvements in Child-Pugh score. It is recommended to initiate active systemic therapy early in patients with CP B cirrhosis to maximize patient benefits.