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.

中文翻译：

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一线 PD-1/PD-L1 抑制剂组合治疗广泛期小细胞肺癌的疗效和安全性：贝叶斯网络荟萃分析。

目的 几项随机对照试验 (RCT) 表明，一线程序性细胞死亡蛋白 1/死亡配体 1 抑制剂联合化疗（PD-1/PD-L1 + 化疗）可带来广泛期小细胞肺的生存获益癌症（ES-SCLC）与铂类化疗相比。本研究旨在确定最佳的 PD-1/PD-L1 + 化疗组合策略。方法 我们纳入了比较 ES-SCLC 中 PD-1/PD-L1 + 化疗与单独化疗的随机对照试验。考虑了总生存期 (OS)、无进展生存期 (PFS)、客观缓解率 (ORR) 和⩾3 级治疗相关不良事件。提取比值比 (OR)、风险比 (HR) 及其 95% 置信区间 (CI)。结果 贝叶斯网络荟萃分析对 6 项随机对照试验进行了分析，涉及 2600 名患者。结果显示，化疗中添加 PD-1/PD-L1 抑制剂可显着改善 OS（HR = 0.72，95% CI：0.66-0.79）、PFS（HR = 0.69，95% CI：0.63-0.75）和ORR（OR = 1.32，95% CI：1.12-1.56），未发现毒性差异（OR = 1.09，95% CI：0.92-1.30）。发现 Serplulimab 加化疗可提供最佳 OS（HR = 0.63，95% CI：0.49-0.82）、最佳 PFS（HR = 0.47，95% CI：0.38-0.59）和最佳 ORR（OR = 1.7， 95% CI：1.15-2.53）。此外，虽然 PD-L1 + 化疗和 PD-1 + 化疗之间在 OS（HR = 0.99，95% CI：0.91-1.08）和 ORR（OR = 1.27，95% CI：0.91-1.78）方面没有差异，与 PD-L1 + 化疗相比，PD-1 + 化疗在 PFS 方面显示出显着的益处（HR = 0.82，95% CI：0.68-0.98）。结论 Serplulimab 联合化疗似乎是 ES-SCLC 患者更好的一线免疫治疗组合。在 PFS 方面，PD-1 + 化疗似乎优于 PD-L1 + 化疗。