Comparative efficacy and safety of novel immuno-chemotherapy for extensive-stage small-cell lung cancer: a network meta-analysis of randomized controlled trial.

Recently, several new first-line immune checkpoint inhibitors (ICIs) plus chemotherapy have been approved for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, direct comparisons between first-line treatments are lacking. Therefore, we indirectly compared the efficacy and safety of specific treatment strategies to inform physicians' and patients' clinical decisions. The Pubmed, Cochrane, Embase, and Web of Science databases were searched from 1 January 2000 to 27 November 2022, for randomized clinical trials (RCTs) assessing first-line immuno-chemotherapies for ES-SCLC. A fixed-effect multivariable meta-regression model was established for frequentist network meta-analysis and hazard ratios (HRs) with 95% confidence intervals (95% CI) were computed to compare the effects of immuno-chemotherapies on patient overall survival (OS) and progression-free survival (PFS), while risk ratios with 95% CI were used for treatment- and immune-related adverse events (AEs). The p score values were then used to rank treatments based on their odds of being the best treatment option. The research protocol was registered with the PROSPERO (CRD42022383254). Seven studies involving 3822 patients were eligible for analysis. Serplulimab plus chemotherapy had better OS outcomes compared to chemotherapy (HR = 0.63; 95% CI: 0.49-0.82) and ipilimumab plus chemotherapy (HR = 0.67; 95% CI: 0.50-0.90). It additionally exhibited better PFS outcomes compared to chemotherapy (HR = 0.48; 95% CI: 0.39-0.60), adebrelimab (HR = 0.72; 95% CI: 0.53-0.97), atezolizumab (HR = 0.62; 0.46-0.85), durvalumab (HR = 0.60; 95% CI: 0.45-0.80), durvalumab and tremelimumab (HR = 0.57; 95% CI: 0.43-0.76), ipilimumab (HR = 0.57; 95% CI: 0.44-0.73), and pembrolizumab (HR = 0.64; 95% CI: 0.48-0.86) plus chemotherapy. Serplulimab plus chemotherapy was linked to the greatest odds of effectively reducing the odds of death (p score = 0.87) and progression (p score = 0.99) while exhibiting a good safety profile. Serplulimab plus chemotherapy exhibited the best survival outcomes with manageable AEs. Thus, serplulimab plus chemotherapy may represent the optimal best first-line treatment option for ES-SCLC patients.