Center of Biotherapy, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China.
Department of Medical Oncology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China.
Thorac Cancer. 2024 Nov;15(33):2375-2385. doi: 10.1111/1759-7714.15458. Epub 2024 Oct 13.
To evaluate the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), we conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and real-world studies (RWS).
By scanning PubMed, Web of science, Embase, and other relevant clinical information public databases, nine RCTs and eight RWSs involving 5205 patients were included in the study. We directly compared the differences between chemotherapy and PD-1/PD-L1 inhibitors plus chemotherapy, and determined the optimal treatment strategy through network meta-analysis (NMA).
Compared to chemotherapy, the addition of PD-1/PD-L1 inhibitors significantly improves the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in SCLC patients. Regarding safety, both RCTs and RWSs indicated no significant difference in grade 3-4 adverse events between chemotherapy and chemoimmunotherapy. NMA showed serplulimab plus chemotherapy (Serp_Chemo) appears to provide the best OS, PFS, and ORR benefit, while nivolumab plus chemotherapy shows higher toxicity than other regimens. In subgroup analysis, for elderly patients (age ≥65) and non-elderly (age <65) patients, the most promising quality regimens for achieving better OS extension are atezolizumab plus chemotherapy (Atez_Chemo) and Serp_Chemo, respectively. For patients with PD-L1 ≥ 1% and lactate dehydrogenase (LDH) > upper limit of normal (ULN), there is no apparent OS benefit from immune therapy.
In ES-SCLC treatment, adding PD-1/PD-L1 inhibitors to standard chemotherapy improves OS, PFS, and ORR, with Serp_Chemo shows the most promise. Atez_Chemo and Serp_Chemo provided better survival for elderly and non-elderly patients, respectively.
评估程序性细胞死亡蛋白 1（PD-1）/程序性细胞死亡配体 1（PD-L1）抑制剂在广泛期小细胞肺癌（ES-SCLC）治疗中的疗效和安全性，我们进行了一项系统评价和荟萃分析，纳入了随机对照试验（RCT）和真实世界研究（RWS）。
通过扫描 PubMed、Web of Science、Embase 和其他相关临床信息公共数据库，纳入了 9 项 RCT 和 8 项 RWS，共纳入 5205 例患者。我们直接比较了化疗与 PD-1/PD-L1 抑制剂联合化疗之间的差异，并通过网络荟萃分析（NMA）确定了最佳治疗策略。
与化疗相比，PD-1/PD-L1 抑制剂的加入显著改善了 SCLC 患者的总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）。关于安全性，RCT 和 RWS 均表明化疗与化疗免疫治疗之间 3-4 级不良事件无显著差异。NMA 显示，serplulimab 联合化疗（Serp_Chemo）似乎提供了最佳的 OS、PFS 和 ORR 获益，而 nivolumab 联合化疗比其他方案毒性更高。亚组分析显示，对于老年（≥65 岁）和非老年（<65 岁）患者，实现更好的 OS 延长的最有前途的高质量方案分别是 atezolizumab 联合化疗（Atez_Chemo）和 Serp_Chemo。对于 PD-L1≥1%和乳酸脱氢酶（LDH）>正常值上限（ULN）的患者，免疫治疗没有明显的 OS 获益。
在 ES-SCLC 治疗中，标准化疗联合 PD-1/PD-L1 抑制剂可提高 OS、PFS 和 ORR，其中 Serp_Chemo 最有前景。Atez_Chemo 和 Serp_Chemo 分别为老年和非老年患者提供了更好的生存。
