免疫检查点抑制剂联合化疗与单纯化疗用于一线治疗低PD-L1表达的晚期胃癌患者的比较：一项系统评价和荟萃分析

Comparison of immune checkpoint inhibitors in combination with chemotherapy versus chemotherapy alone in the first-line treatment of advanced gastric cancer patients with low PD-L1 expression: a systematic review and meta-analysis.

作者信息

Wang Yuxin, Xie Tong, Xiang Shuai, Liu Cheng, Cheng Siyuan, Zhang Bohan, Zhang Yifan, Feng Yang, Wang Yingxuan, Yu Donghe, Gao Hongchao, Gao Erke, Shen Lin, Peng Zhi

机构信息

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.

Department of Pancreatic and Gastric Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Ther Adv Med Oncol. 2025 May 8;17:17588359251336627. doi: 10.1177/17588359251336627. eCollection 2025.

DOI:10.1177/17588359251336627

PMID:40351322

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12062602/

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) + chemotherapy became standard her2-GC first line treatment.

OBJECTIVES

The aim of this study is to investigate whether ICIs + chemo provides benefit for patients with low programmed death-ligand 1 (PD-L1) expression.

DESIGN

This study is a systematic review and meta-analysis.

DATA SOURCES

We searched PubMed, Embase, Web of Science, and Cochrane Library as well as the 2019 to 2024 Annual Meetings of the European Society for Medical Oncology, the American Association for Cancer Research, the American Society of Clinical Oncology (ASCO), and the ASCO Symposium on Gastrointestinal Oncology (ASCO-GI) and the ClinicalTrials.gov database.

METHODS

This systematic review included phase III randomized controlled trials comparing first-line immunotherapy combined with chemotherapy versus chemotherapy alone in advanced gastric cancer. KMSubtraction was used to estimate survival data for those trials that did not report data for the PD-L1 low-expression population.

RESULTS

We included a total of nine randomized clinical trials. In patients with combined positive score (CPS) < 1 and CPS < 5, monoclonal antibody + chemotherapy did not show an improvement in overall survival (OS) or progression-free survival (PFS) (CPS < 1 OS: hazard ratio (HR) = 0.91, 95% CI: 0.77-1.08; PFS: HR = 0.88, 95% CI: 0.73-1.07. CPS < 5 OS: HR = 0.92, 95% CI: 0.79-1.08; PFS: HR = 0.78, 95% CI: 0.53-1.14). However, in trials using dual antibodies, patients with PD-L1 CPS < 5 achieved improvements in PFS (HR = 0.64, 95% CI: 0.52-0.80). In trials using tumor area positivity (TAP) scoring, the subgroup with TAP < 5% did not achieve benefits in OS or PFS from immunotherapy plus chemotherapy (OS: HR = 0.92, 95% CI: 0.75-1.13; PFS: HR = 0.91, 95% CI: 0.74-1.13).

CONCLUSION

Our study results indicate that in the first-line treatment of advanced gastric cancer, monoclonal antibody combined with chemotherapy does not provide a survival benefit compared to chemotherapy alone for patients with low PD-L1 expression. However, it is noteworthy that in the COMPASSION-15 trial, patients with CPS < 5 achieve significant improvements in OS and PFS, which may be related to the bispecific antibodies and needs to be validated by further studies.

TRIAL REGISTRATION

This study was registered in PROSPERO (CRD42024568972).

摘要

背景

免疫检查点抑制剂（ICIs）联合化疗成为人表皮生长因子受体2（HER2）阴性晚期胃癌（GC）的一线标准治疗方案。

目的

本研究旨在探讨ICIs联合化疗对程序性死亡配体1（PD-L1）低表达患者是否有益。

设计

本研究为系统评价和荟萃分析。

数据来源

我们检索了PubMed、Embase、Web of Science和Cochrane图书馆，以及2019年至2024年欧洲医学肿瘤学会、美国癌症研究协会、美国临床肿瘤学会（ASCO）、ASCO胃肠道肿瘤研讨会（ASCO-GI）的年会以及ClinicalTrials.gov数据库。

方法

本系统评价纳入了比较一线免疫治疗联合化疗与单纯化疗治疗晚期胃癌的III期随机对照试验。对于未报告PD-L1低表达人群数据的试验，采用KMSubtraction法估计生存数据。

结果

我们共纳入了9项随机临床试验。在联合阳性评分（CPS）<1和CPS<5的患者中，单克隆抗体联合化疗在总生存期（OS）或无进展生存期（PFS）方面未显示出改善（CPS<1：OS：风险比（HR）=0.91，95%置信区间（CI）：0.77-1.08；PFS：HR=0.88，95%CI：0.73-1.07。CPS<5：OS：HR=0.92，95%CI：0.79-1.08；PFS：HR=0.78，95%CI：0.53-1.14）。然而，在使用双特异性抗体的试验中，PD-L1 CPS<5的患者在PFS方面有改善（HR=0.64，95%CI：0.52-0.80）。在使用肿瘤区域阳性（TAP）评分的试验中，TAP<5%的亚组在免疫治疗联合化疗的OS或PFS方面未获得益处（OS：HR=0.92，95%CI：0.75-1.13；PFS：HR=0.91，95%CI：0.74-1.13）。