The benefits and risks of adding PD-1/PD-L1 inhibitors to chemotherapy for stage IIIb-IV non-small-cell lung cancer: an updated meta-analysis based on phase 3 randomized controlled trials.

IF 3.5 3区 医学 Q2 ONCOLOGY
Frontiers in Oncology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI:10.3389/fonc.2025.1590017
Yun Xu, Baoliang Zhong, Chunlin Yu, Qingjian Hou, Wenying Chen, Wen Zheng, Wenxiong Zhang, Tonggang Zhou
{"title":"The benefits and risks of adding PD-1/PD-L1 inhibitors to chemotherapy for stage IIIb-IV non-small-cell lung cancer: an updated meta-analysis based on phase 3 randomized controlled trials.","authors":"Yun Xu, Baoliang Zhong, Chunlin Yu, Qingjian Hou, Wenying Chen, Wen Zheng, Wenxiong Zhang, Tonggang Zhou","doi":"10.3389/fonc.2025.1590017","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Previous research has confirmed that integrating PD-1/PD-L1 inhibitors with chemotherapy (PC) represents a more effective strategy for treating advanced non-small-cell lung cancer (NSCLC). However, with the increasing number of phase 3 randomized controlled trials (RCTs) published in recent years, it is essential to re-evaluate the validity of this conclusion and to comprehensively assess the efficacy and safety across diverse patient subgroups.</p><p><strong>Methods: </strong>We systematically reviewed phase 3 RCTs comparing PC with chemotherapy alone for stage IIIb-IV NSCLC. Data were extracted and analyzed for overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs). Subgroup analyses were performed based on factors such as disease stage, pathological type, etc.</p><p><strong>Results: </strong>After screening, 19 phase 3 RCTs involving 9335 patients were included. Our updated analysis confirmed at PC therapy significantly improves OS (hazard ratio [HR]: 0.73 [0.69, 0.77], P < 0.00001), PFS (HR: 0.56 [0.52, 0.60], P < 0.00001), duration of response (DOR, HR: 0.50 [0.45, 0.54], P < 0.00001) and objective response rate (ORR, risk ratio [RR]: 1.59 [1.51, 1.67], P < 0.00001) compared to chemotherapy alone. The survival benefits were consistent across all subgroups and increases with longer follow-up. Brain metastases and PD-L1 combined positive score (CPS) > 50% were the favorable factors for PC group. However, the combined treatment was associated with an increased incidence of total/grade 3-5 treatment emergent AEs (TEAEs), and immune-related AEs (irAEs), although the overall safety profile remained manageable. The most common AEs in the PC group were blood toxicity related AEs (anemia, neutrophil count decreased, etc).</p><p><strong>Conclusion: </strong>The PC therapy continues to provide a substantial survival benefit for patients with stage IIIb-IV NSCLC. However, its higher incidence of AEs, especially irAEs, needs to be taken seriously.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD420251005925, identifier CRD420251005925.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1590017"},"PeriodicalIF":3.5000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460147/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fonc.2025.1590017","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Previous research has confirmed that integrating PD-1/PD-L1 inhibitors with chemotherapy (PC) represents a more effective strategy for treating advanced non-small-cell lung cancer (NSCLC). However, with the increasing number of phase 3 randomized controlled trials (RCTs) published in recent years, it is essential to re-evaluate the validity of this conclusion and to comprehensively assess the efficacy and safety across diverse patient subgroups.

Methods: We systematically reviewed phase 3 RCTs comparing PC with chemotherapy alone for stage IIIb-IV NSCLC. Data were extracted and analyzed for overall survival (OS), progression-free survival (PFS), response rates, and adverse events (AEs). Subgroup analyses were performed based on factors such as disease stage, pathological type, etc.

Results: After screening, 19 phase 3 RCTs involving 9335 patients were included. Our updated analysis confirmed at PC therapy significantly improves OS (hazard ratio [HR]: 0.73 [0.69, 0.77], P < 0.00001), PFS (HR: 0.56 [0.52, 0.60], P < 0.00001), duration of response (DOR, HR: 0.50 [0.45, 0.54], P < 0.00001) and objective response rate (ORR, risk ratio [RR]: 1.59 [1.51, 1.67], P < 0.00001) compared to chemotherapy alone. The survival benefits were consistent across all subgroups and increases with longer follow-up. Brain metastases and PD-L1 combined positive score (CPS) > 50% were the favorable factors for PC group. However, the combined treatment was associated with an increased incidence of total/grade 3-5 treatment emergent AEs (TEAEs), and immune-related AEs (irAEs), although the overall safety profile remained manageable. The most common AEs in the PC group were blood toxicity related AEs (anemia, neutrophil count decreased, etc).

Conclusion: The PC therapy continues to provide a substantial survival benefit for patients with stage IIIb-IV NSCLC. However, its higher incidence of AEs, especially irAEs, needs to be taken seriously.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251005925, identifier CRD420251005925.

在iii期b- iv期非小细胞肺癌化疗中加入PD-1/PD-L1抑制剂的获益和风险:基于3期随机对照试验的最新荟萃分析
背景:先前的研究已经证实,PD-1/PD-L1抑制剂联合化疗(PC)是治疗晚期非小细胞肺癌(NSCLC)更有效的策略。然而,随着近年来发表的3期随机对照试验(rct)越来越多,有必要重新评估这一结论的有效性,并全面评估不同患者亚组的疗效和安全性。方法:我们系统地回顾了比较PC与单独化疗治疗iib - iv期NSCLC的3期随机对照试验。提取数据并分析总生存期(OS)、无进展生存期(PFS)、缓解率和不良事件(ae)。根据疾病分期、病理类型等因素进行亚组分析。结果:经筛选,纳入3期rct 19项,共9335例患者。我们的最新分析证实,与单独化疗相比,PC治疗显著改善了OS(风险比[HR]: 0.73 [0.69, 0.77], P < 0.00001)、PFS(风险比[HR]: 0.56 [0.52, 0.60], P < 0.00001)、缓解时间(DOR,风险比[HR]: 0.50 [0.45, 0.54], P < 0.00001)和客观缓解率(风险比[RR]: 1.59 [1.51, 1.67], P < 0.00001)。所有亚组的生存获益都是一致的,并且随着随访时间的延长而增加。脑转移和PD-L1联合阳性评分(CPS) bbb50 %是PC组的有利因素。然而,联合治疗与总/ 3-5级治疗突发事件(teae)和免疫相关事件(irAEs)的发生率增加有关,尽管总体安全性仍然可控。PC组最常见的不良反应是血液毒性相关的不良反应(贫血、中性粒细胞计数减少等)。结论:PC治疗继续为iib - iv期NSCLC患者提供实质性的生存益处。然而,其较高的ae发病率,特别是ae,需要认真对待。系统综述注册:https://www.crd.york.ac.uk/PROSPERO/view/CRD420251005925,标识符CRD420251005925。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Frontiers in Oncology
Frontiers in Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
6.20
自引率
10.60%
发文量
6641
审稿时长
14 weeks
期刊介绍: Cancer Imaging and Diagnosis is dedicated to the publication of results from clinical and research studies applied to cancer diagnosis and treatment. The section aims to publish studies from the entire field of cancer imaging: results from routine use of clinical imaging in both radiology and nuclear medicine, results from clinical trials, experimental molecular imaging in humans and small animals, research on new contrast agents in CT, MRI, ultrasound, publication of new technical applications and processing algorithms to improve the standardization of quantitative imaging and image guided interventions for the diagnosis and treatment of cancer.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信