Efficacy of PD-1/PD-L1 inhibitors in advanced hepatocellular carcinoma: A systematic review and meta-analysis

A BSTRACT Objectives: This study aimed to investigate the efficacy and safety of programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: PubMed, EMBASE, and the Cochrane Library were searched for articles published until November 2022. Studies reporting the efficacy of PD-1/PD-L1 inhibitors in patients with advanced HCC were eligible for inclusion. The outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and ≥ Grade 3 treatment-related adverse events (TrAEs). Results: Fourteen trials with 4515 patients with HCC were included. Our results showed that treatment with PD-1/PD-L1 inhibitors was associated with better ORR and DCR than that with control (placebo or sorafenib or lenvatinib) (odds ratio [OR], 3.89; 95% confidence interval (CI), 2.55–5.95 and OR, 1.47; 95% CI, 1.11–1.95, respectively). The overall hazard ratio (HR) of PFS and OS were 0.66 (95% CI 0.56–0.78) and 0.65 (95% CI 0.55–0.77), respectively. In subgroup analysis, PD-1/PD-L1 inhibitor combination therapy had an advantage in terms of PFS (HR: 0.57 vs. 0.81) compared to that of PD-1/PD-L1 monotherapy. The incidence of grade 3–5 TrAEs was not significantly higher with PD-1/PD-L1 inhibitors than that with the control (OR, 1.12; 95% CI, 0.70–1.81). However, the combination of PD-1inhibitor with higher incidence of Grade 3–5 TrAEs (OR: 2.04, 95% CI 0.66–6.32) than the combination PD-L1 inhibitor (OR: 0.95, 95% CI 0.50–1.81). Conclusion: The combination of PD-1/PD-L1 inhibitors and targeted agents significantly improved the clinical outcomes in patients with advanced HCC. However, the incidence of Grade 3–5 TrAEs with PD-1 inhibitor combination therapy was higher than the combination PD-L1 inhibitor.