PD-1/PD-L1 Inhibitors Plus Antiangiogenic Drugs Versus Sorafenib as the First Line Treatment for Advanced Hepatocellular Carcinoma: A Phase 3 RCTs Based Meta-Analysis

Abstract

Background For advanced hepatocellular carcinoma (HCC), sorafenib remains the established therapy. PD-1/PD-L1 inhibitors plus antiangiogenic drugs (PIAD) as a new therapeutic approach for advanced HCC is still a subject of clinical debate regarding whether they offer improved treatment outcomes. This study was conducted to compare the two treatments in terms of antitumor efficacy and safety. Methods Randomized controlled trials (RCTs) comparing PIAD and sorafenib for advanced HCC were retrieved from six databases. Survival (overall survival [OS] and progression-free survival [PFS]) were the main outcomes measured. Secondary endpoints included responses, adverse events (AEs), and effects on quality of life. Results Seven studies based on four RCTs (CARES-310, COSMIC-312, IMbrave150, and ORIENT-32) were included. The PIAD group exhibited better OS (hazard ratio [HR]: 0.69, 95% confidence interval [CI]: [0.53, 0.89], P = 0.005), and PFS (HR: 0.60, 95% CI: [0.53, 0.67], P < 0.00001). The survival advantages of OS and PFS were confirmed in almost all subgroups. The PIAD group exhibited higher OS rates at 6–18 months and PFS rates at 6–12 months. Additionally, the objective response rate, disease control rate, complete response, and partial response were higher in PIAD group. The PIAD group had a delayed decline in quality of life, physical functioning, and role functioning. However, the PIAD group experienced more grades 3–5 and serious AEs, along with treatment discontinuation, dose reduction, and dose interruption. Conclusions PIAD appears to be better than sorafenib for advanced HCC with better survival and responses. However, its higher rate of AEs requires cautious attention.