Approved immune checkpoint inhibitors in hepatocellular carcinoma: a large-scale meta-analysis and systematic review

Purpose: A meta-analysis was performed to assess the benefits and safety profile of approved immune checkpoint inhibitors in hepatocellular carcinoma patients. Methods: Eligible studies were searched from Cochrane, Embase, and PubMed databases based on a well-established strategy. Review manager version 5.4 was employed for data analysis. Results: Following the exclusion of ineligible studies, eight studies were included in this meta-analysis. Compared with control group, immune checkpoint inhibitors were associated with improved ORR (OR 3.65, 95% CI 2.82–4.73, P  < 0.00001), DCR (OR 1.17, 95% CI 1.02–1.35, P  = 0.02), SD (OR 0.72, 95% CI 0.58–0.89, P  = 0.002), and more risk of all caused any-grade adverse events (OR 1.64, 95% CI 1.03–2.60, P  = 0.004). However, no significant differences were observed in PD (OR 0.96, 95% CI 0.82–1.12, P  = 0.59), OS (HR 0.76, 95% CI 0.66–0.87, P  = 0.25), PFS (HR 0.74, 95% CI 0.63–0.87, P  = 0.24) and all caused grade 3 or 4 adverse events (OR 1.22, 95% CI 0.98–1.52, P  = 0.07), treatment-related any grade adverse events (OR 0.99, 95% CI 0.48–2.07, P  = 0.98), treatment-related grade 3 or 4 events (OR 1.05, 95% CI 0.81–1.35, P  = 0.72) between the two groups. After studies with nivolumab as a monotherapy excluded, patients in the immune checkpoint inhibitor group showed significant improvements in OS (HR 0.67, 95% CI 0.58–0.77, P  < 0.00001) and PFS (HR 0.62, 95% CI 0.54–0.71, P  < 0.00001). Conclusion: Immune checkpoint inhibitors have demonstrated peculiar benefits in the treatment of HCC with an acceptable safety profile. Combining immune checkpoint inhibitors with other medications may be more beneficial for patients with hepatocellular carcinoma.