Tzu‑Rong Peng, Li‑Jou Yang, Ta‑Wei Wu*
Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
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.
Keywords: Hepatocellular carcinoma, Meta‑analysis, Programmed cell death‑1, Programmed death ligand 1
