Efficacy and safety of first-line immunotherapy-based regimens for patients with extensive-stage small cell lung cancer: a systematic review and network meta-analysis.

IF 3.5 2区 医学 Q2 ONCOLOGY Translational lung cancer research Pub Date : 2025-01-24 Epub Date: 2025-01-22 DOI:10.21037/tlcr-24-636
Wengang Zhang, Wencheng Zhao, Xinyu Zhang, Zhiyi Guo, Li Ye, Zhimin Chen, Kandi Xu, Lishu Zhao, Xinyue Liu, Yujin Liu, Hao Wang, Yayi He
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Abstract

Background: Combination regimens of immunotherapy plus chemotherapy have been approved as the first-line and standard of care for extensive-stage small cell lung cancer (ES-SCLC). Novel regimens are continuously being explored, with the ETER701 study being the representative randomized controlled trial (RCT). ETER701 study has assessed the efficacy and safety of chemotherapy with or without anlotinib (multi-target angiogenesis inhibitor) + benmelstobart (programmed cell death ligand 1 inhibitor) (Anl/Ben/CT). There is no evidence-based medicine available proving that Anl/Ben/CT is the optimal regimen due to the lack of direct or indirect comparisons among varying immunotherapy-based regimens. In this study, we aimed to identify the optimal regimen to assist in clinical decision-making.

Methods: The eligible RCTs were identified by searching PubMed, Embase, Cochrane Library databases, and major international conferences. Then, the network meta-analysis was analyzed to compare the efficacy and safety among 15 first-line regimens in ES-SCLC. The Cochrane Risk of Bias Tool was used to assess the risk of bias in included studies.

Results: A total of 12 immunotherapy-related RCTs covering 15 interventions and 6,178 patients with ES-SCLC were included. Overall, most RCTs exhibited a low risk of bias across multiple domains. The results indicated that most immunotherapy-based regimens could significantly prolong progression-free survival (PFS) compared with chemotherapy alone, especially Anl/Ben/CT [hazard ratio (HR) 0.32, 95% confidence interval (CI): 0.25-0.40]. Similar results were observed regarding overall survival (OS), that is, most immunotherapy-related regimens dramatically reduced the risk of death in ES-SCLC, with Anl/Ben/CT being the most prominent (HR 0.61, 95% CI: 0.47-0.80). The Bayesian ranking probabilities showed that Anl/Ben/CT ranked first and serplulimab plus chemotherapy ranked second in both PFS and OS among 15 regimens. Regarding safety, Anl/Ben/CT ranked 3rd, and serplulimab plus chemotherapy ranked 7th.

Conclusions: Adding anlotinib and benmelstobart to chemotherapy significantly improved PFS and OS compared with chemotherapy alone or chemotherapy plus immunotherapy, with an acceptable safety profile in patients with ES-SCLC. In conclusion, Anl/Ben/CT could be a new, preferable first-line treatment option but further clinical studies are needed to validate its efficacy and safety.

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基于免疫治疗的一线方案对大分期小细胞肺癌患者的疗效和安全性:一项系统综述和网络荟萃分析
背景:免疫治疗加化疗联合方案已被批准为广泛期小细胞肺癌(ES-SCLC)的一线和标准治疗方案。新的治疗方案不断被探索,以ETER701研究为代表性的随机对照试验(RCT)。ETER701研究评估了化疗联合或不联合anlotinib(多靶点血管生成抑制剂)+ benmelstobart(程序性细胞死亡配体1抑制剂)(Anl/Ben/CT)的疗效和安全性。由于缺乏对不同免疫治疗方案的直接或间接比较,目前尚无循证医学证明Anl/Ben/CT是最佳方案。在这项研究中,我们旨在确定最佳方案,以协助临床决策。方法:通过检索PubMed、Embase、Cochrane Library数据库和主要国际会议,筛选符合条件的rct。然后进行网络meta分析,比较15种ES-SCLC一线治疗方案的疗效和安全性。采用Cochrane偏倚风险工具评估纳入研究的偏倚风险。结果:共纳入12项免疫治疗相关的随机对照试验,涵盖15种干预措施,6178例ES-SCLC患者。总体而言,大多数随机对照试验在多个领域表现出较低的偏倚风险。结果显示,与单独化疗相比,大多数基于免疫治疗的方案可显著延长无进展生存期(PFS),尤其是Anl/Ben/CT[风险比(HR) 0.32, 95%可信区间(CI): 0.25-0.40]。在总生存率(OS)方面也观察到类似的结果,即大多数免疫治疗相关方案显著降低ES-SCLC的死亡风险,其中Anl/Ben/CT最为显著(HR 0.61, 95% CI: 0.47-0.80)。贝叶斯排序概率显示,在15个方案中,Anl/Ben/CT方案的PFS和OS均排名第一,serplulimab +化疗方案排名第二。安全性方面,Anl/Ben/CT排名第3,serpluliumab联合化疗排名第7。结论:与单独化疗或化疗加免疫治疗相比,化疗中加入anlotinib和benmelstobart可显著改善PFS和OS,并且在ES-SCLC患者中具有可接受的安全性。综上所述,Anl/Ben/CT可能是一种新的、较好的一线治疗方案,但需要进一步的临床研究来验证其有效性和安全性。
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来源期刊
CiteScore
7.20
自引率
2.50%
发文量
137
期刊介绍: Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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