Clinical outcomes of PD-1/PD-L1 inhibitors in patients with advanced hepatocellular carcinoma: a systematic review and meta-analysis

Purpose Programmed death ligand 1(PD-L1)/programmed cell death-1(PD-1) inhibitors have shown promising efficacy in unresectable patients with advanced hepatocellular carcinoma (HCC), but the results are not consistent. Our goal was to evaluate the safety and efficacy of PD-L1/PD-1 inhibitors or plus anti-CTLA-4 antibody or anti-VEGF agents for the treatment of unresectable HCC. Methods Cochrane library, Embase, and PubMed were searched till August 2021. Data on progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and disease control rate (DCR) were pooled and analyzed by Stata14 software. Results Thirteen prospective trials with 2,386 HCC patients were included. Pooled analysis estimated an ORR of about 0.21 (95% CI = 0.18-0.25) and a DCR of 0.59 (95% CI = 0.52-0.65) for anti-PD-1/PD-L1 therapy. Summary PFS was 4.19 (95% CI = 3.31-5.18) months and summary OS was 13.23 (95% CI = 12.06-14.41) months. After using PD-L1/PD-1 inhibitors plus anti-VEGF agents, ORR was 0.26 (95% CI = 0.20-0.33), DCR was 0.75 (95% CI = 0.69-0.81) and PFS was 6.2 (95% CI = 4.61-7.78) months. PD-L1/PD-1 inhibitors plus anti-CTLA-4 antibody therapy achieved an ORR of 0.23 (95% CI = 0.14-0.33), an DCR of 0.44 (95% CI = 0.39-0.50) and a PFS of 1.88 (95% CI = 1.51-2.26). Conclusions PD-L1/PD-1 inhibitors were effective and tolerable in patients with advanced HCC. Furthermore, compared with anti-PD-1/PD-L1 monotherapy, PD-L1/PD-1 inhibitors plus anti-VEGF agents resulted in more clinical improvements in ORR, DCR, and PFS.