Efficacy and safety comparisons of PD-1 versus PD-L1 inhibitors in patients with solid cancer: a systematic review and meta-analysis

A comprehensive evaluation between PD-1 and PD-L1 inhibitors is critical for appropriate treatment choice. To evaluate the efficacy and safety of PD-1 and PD-L1 inhibitors, this meta-analysis was conducted through adjusted indirect comparison. Systematic literature search was conducted in PubMed, Embase, and Cochrane Central databases from January 1st 2000 to January 31st 2023. Randomized controlled trials (RCT) comparing PD-1/PD-L1 inhibitors with standard treatments in solid tumors were retrieved. Eligible RCTs regarding PD-1/PD-L1 inhibitors were matched as mirror groups according to the same population and study design. Hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and disease-free/event-free survival (DFS/EFS), and risk ratio (RR) for objective response rate (ORR) and adverse events (AEs) were generated from indirect comparisons in each mirror group and pooled for overall meta-analysis. In total, 96 eligible RCTs with 104 arms of 56,597 patients were identified to construct 32 mirror groups. Patients treated with PD-1 inhibitors exhibited improved OS (HR, 0.86 [95% CI: 0.81, 0.90]; P < 0.001), PFS (HR, 0.85 [95% CI: 0.75, 0.96]; P = 0.01), and DFS/EFS (HR, 0.81 (95% CI: 0.70, 0.94]; P = 0.005) in all populations compared with those with PD-L1 inhibitors, together with a higher ORR (RR, 1.12 [95% CI: 1.04, 1.20]; P = 0.002). While PD-1 inhibitors showed comparable rates of treatment-related AEs with PD-L1 inhibitors, PD-1 inhibitors demonstrated a higher discontinuation rate due to treatment-related AEs (RR, 2.27 [95% CI: 1.91, 2.70]; P < 0.0001). This meta-analysis revealed that PD-1 inhibitors exhibited better survival outcomes compared with PD-L1 inhibitors in solid tumors with comparable safety profiles except for a higher discontinuation rate. This systematic review was registered in PROSPERO as CRD42023452639.