Efficacy and safety of first-line PD-1/PD-L1 inhibitor combinations for extensive-stage small-cell lung cancer: a Bayesian network meta-analysis

Objectives:Several randomized controlled trials (RCTs) indicated that first-line programmed cell death protein-1/death-ligand 1 inhibitors plus chemotherapy (PD-1/PD-L1 + chemo) led to survival benefits in extensive-stage small-cell lung cancer (ES-SCLC) compared with platinum-based chemotherapy. This study aims to identify the optimal PD-1/PD-L1 + chemo combination strategy.Methods:We included RCTs comparing PD-1/ PD-L1 + chemo versus chemo alone in ES-SCLC. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade > 3 treatment-related adverse events were considered. Odds ratios (ORs), hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted.Results:Six RCTs with 2600 patients were analyzed in this Bayesian network meta-analysis. Results showed that adding PD-1/PD-L1 inhibitors to chemotherapy led to significant benefits in OS (HR = 0.72, 95% CI: 0.66-0.79), PFS (HR = 0.69, 95% CI: 0.63-0.75), and ORR (OR = 1.32, 95% CI: 1.12-1.56), and no differences in toxicity were found (OR = 1.09, 95% CI: 0.92-1.30). Serplulimab plus chemotherapy was found to provide the best OS (HR = 0.63, 95% CI: 0.49-0.82), the best PFS (HR = 0.47, 95% CI: 0.38-0.59), and the best ORR (OR = 1.7, 95% CI: 1.15-2.53). Moreover, although there were no difference between PD-L1 + chemo and PD-1 + chemo regarding OS (HR = 0.99, 95% CI: 0.91-1.08) and ORR (OR = 1.27, 95% CI: 0.91-1.78), PD-1 + chemo showed a significant benefit in PFS (HR = 0.82, 95% CI: 0.68-0.98) compared with PD-L1 + chemo.Conclusions:Serplulimab plus chemotherapy seems to be superior first-line immunotherapy combination for patients with ES-SCLC. PD-1 + chemo seems to outperform PD-L1 + chemo in PFS.