Zhou Linjing, Li Yuwei, Wang Le, Chen Kaiyan, Zhou Shichao, Chen Yunfei, Sun Jing, Tong Yunfeng, Fan Yun
Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Ther Adv Med Oncol. 2025 Jun 25;17:17588359251348310. doi: 10.1177/17588359251348310. eCollection 2025.
Immune checkpoint inhibitors (ICIs) combined with chemotherapy, with or without angiogenesis inhibitors, have been investigated as the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, it remains unclear which treatment modalities are the most effective and safest, as comparative studies evaluating these treatment options are limited.
This article aims to compare the relative efficacy and safety of ICIs + Chemo + angiogenesis inhibitors versus ICIs + Chemo as the first-line treatment for ES-SCLC.
A network meta-analysis was conducted to systematically compare the efficacy and safety data obtained from various clinical trials.
This study presents a systematic review and Bayesian network meta-analysis of data sourced from PubMed, Cochrane Library, EMBASE, ClinicalTrials.gov, and major international conferences up to August 31, 2024. Furthermore, this study analyzed both published works and gray literature on randomized clinical trials (RCTs).
A comprehensive analysis was conducted on 10 phase III RCTs comprising 2672 untreated ES-SCLC patients treated with two PD-L1 inhibitor combinations with angiogenesis inhibitors (ICIs + Chemo + angiogenesis) and eight PD-1/PD-L1 inhibitor combinations (ICIs + Chemo). Patients treated with ICIs + Chemo + angiogenesis inhibitors had higher progression-free survival (PFS) (hazard ratio (HR) = 0.56, 95% CI: 0.47-0.66) and overall response rate (ORR) (OR = 1.64, 95% CI: 1.17-2.31) compare to those who were treated with ICIs + Chemo. However, no significant difference was observed in the overall survival (OS; HR = 0.97, 95% CI: 0.79-1.19) and Grade ⩾ 3 adverse events (OR = 1.28, 95% CI: 0.81-2.04) between these patients. The subgroup analyses revealed that the addition of angiogenesis inhibitors improved the OS in patients under 65 years. Moreover, PFS was improved in all subgroups except the central nervous system metastasis.
This study revealed that first-line immunochemotherapy combined with angiogenesis inhibitors improves PFS and ORR in ES-SCLC patients; however, it did not affect OS. Therefore, it was inferred that patients under the age of 65 can gain survival benefits from the addition of anti-angiogenic therapy.
INPLASY (INPLASY2023110061).
免疫检查点抑制剂（ICIs）联合化疗，无论是否联合血管生成抑制剂，已被研究作为广泛期小细胞肺癌（ES-SCLC）的一线治疗方案。然而，由于评估这些治疗选择的比较研究有限，哪种治疗方式最有效和最安全仍不清楚。
本文旨在比较ICIs+化疗+血管生成抑制剂与ICIs+化疗作为ES-SCLC一线治疗的相对疗效和安全性。
进行网络荟萃分析以系统比较从各种临床试验中获得的疗效和安全性数据。
本研究对截至2024年8月31日从PubMed、Cochrane图书馆、EMBASE、ClinicalTrials.gov和主要国际会议获取的数据进行了系统评价和贝叶斯网络荟萃分析。此外，本研究分析了关于随机临床试验（RCT）的已发表作品和灰色文献。
对10项III期RCT进行了综合分析，这些试验包括2672例未经治疗的ES-SCLC患者，他们接受了两种联合血管生成抑制剂的PD-L1抑制剂组合（ICIs+化疗+血管生成）和8种PD-1/PD-L1抑制剂组合（ICIs+化疗）治疗。与接受ICIs+化疗的患者相比，接受ICIs+化疗+血管生成抑制剂治疗的患者具有更高的无进展生存期（PFS）（风险比（HR）=0.56，95%置信区间：0.47-0.66）和总缓解率（ORR）（OR=1.64，95%置信区间：1.17-2.31）。然而，这些患者在总生存期（OS；HR=0.97，95%置信区间：0.79-1.19）和≥3级不良事件（OR=1.28，95%置信区间：0.81-2.04）方面未观察到显著差异。亚组分析显示，添加血管生成抑制剂可改善65岁以下患者的OS。此外，除中枢神经系统转移外，所有亚组的PFS均有所改善。
本研究表明，一线免疫化疗联合血管生成抑制剂可改善ES-SCLC患者的PFS和ORR；然而，它不影响OS。因此，推断65岁以下患者可从添加抗血管生成治疗中获得生存益处。
INPLASY（INPLASY2023110061）
