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

• Published in: Technology in cancer research & treatment Vol. 23; p. 15330338241305700
• Main Authors: Li, Jun, Liao, Chun, Liu, Zhaohui, Xiong, Hu, Cai, Jing, Liu, Tiande
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2024; Sage Publications Ltd; SAGE Publishing
• Subjects: Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Antiangiogenic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antitumor activity; B7-H1 Antigen - antagonists & inhibitors; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Clinical trials; Clinical Trials, Phase III as Topic; Combination Strategies and Personalized Therapeutic Strategies for Cancer Treatment; Disease control; Drug dosages; Evidence; Hepatocellular carcinoma; Humans; Immune Checkpoint Inhibitors - administration & dosage; Immune Checkpoint Inhibitors - adverse effects; Inhibitor drugs; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Neoplasm Staging; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Quality of Life; Randomized Controlled Trials as Topic; Sorafenib - administration & dosage; Sorafenib - adverse effects; Survival; Targeted cancer therapy; Treatment Outcome; antiangiogenic drugs; meta-analysis; PD-1/PD-L1 inhibitors; sorafenib; hepatocellular carcinoma
• DOI: 10.1177/15330338241305700
• ISSN: 1533-0346; 1533-0338

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.