Background 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. Methods 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). Results 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. Conclusion 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.

中文翻译：

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新型免疫化疗治疗广泛期小细胞肺癌的疗效和安全性比较：随机对照试验的网络荟萃分析。

背景 最近，几种新的一线免疫检查点抑制剂（ICIs）联合化疗已被批准用于治疗广泛期小细胞肺癌（ES-SCLC）患者。然而，缺乏一线治疗之间的直接比较。因此，我们间接比较了特定治疗策略的有效性和安全性，为医生和患者的临床决策提供信息。方法 检索了 2000 年 1 月 1 日至 2022 年 11 月 27 日期间 Pubmed、Cochrane、Embase 和 Web of Science 数据库中评估 ES-SCLC 一线免疫化疗的随机临床试验 (RCT)。建立固定效应多变量元回归模型进行频率网络荟萃分析，并计算具有 95% 置信区间 (95% CI) 的风险比 (HR)，以比较免疫化疗对患者总生存 (OS) 的影响和无进展生存期 (PFS)，而 95% CI 的风险比用于治疗和免疫相关的不良事件 (AE)。然后使用 p 得分值根据成为最佳治疗选择的几率对治疗进行排名。该研究方案已在 PROSPERO 注册（CRD42022383254）。结果 涉及 3822 名患者的 7 项研究符合分析条件。与化疗（HR = 0.63；95% CI：0.49-0.82）和伊匹单抗加化疗（HR = 0.67；95% CI：0.50-0.90）相比，Serplulimab 加化疗具有更好的 OS 结局。与化疗 (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 相比，它还表现出更好的 PFS 结果（HR = 0.60；95% CI：0.45-0.80）、durvalumab 和曲美木单抗（HR = 0.57；95% CI：0.43-0.76）、伊匹单抗（HR = 0.57；95% CI：0.44-0.73）和派姆单抗（HR = 0.57；95% CI：0.44-0.73） = 0.64；95% CI：0.48-0.86）加化疗。Serplulimab 联合化疗与有效降低死亡（p 值 = 0.87）和进展（p 值 = 0.99）的几率最大相关，同时表现出良好的安全性。结论 Serplulimab 联合化疗表现出最佳的生存结果，且 AE 可控。因此，serplulimab 联合化疗可能代表 ES-SCLC 患者的最佳一线治疗选择。