SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1651176
Long-term Outcomes of PD-1 Inhibitors Plus Chemotherapy as First-Line Treatment for Advanced HER2-negative Gastric Cancer: An updated Systematic Review and Meta-Analysis
Provisionally accepted
- Guangxi University of Science and Technology, Liuzhou, China
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Introduction This meta-analysis was designed to compare the long-term outcomes of first-line programmed cell death protein 1 (PD-1) inhibitors plus chemotherapy versus chemotherapy in patients with advanced HER2-negative gastric cancer (GC). Materials and Methods Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched for randomized controlled trials (RCTs) comparing first-line PD-1 inhibitors plus chemotherapy to chemotherapy in patients with advanced HER2-negative GC. The search was conducted from the databases establishment to October 11, 2025. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), treatment-related adverse events (TRAEs), and Grade≥3 TRAEs were subjected to meta-analyses. Results Six RCTs were included in the meta-analysis. The meta-analysis included a group of 6038 patients diagnosed with untreated advanced HER2-negative GC. Within this cohort, 3026 patients were administered first-line PD-1 inhibitors together with chemotherapy, while 3012 patients received first-line chemotherapy alone. Compared with chemotherapy, first-line PD-1 inhibitors plus chemotherapy yielded superior OS (HR= 0.91; 95% CI 0.89 to 0.93; P<0.01), PFS (HR= 0.89, 95%CI 0.87 to 0.91 P<0.01), and ORR (RR= 1.22, 95% CI, 1.16 to 1.29, P<0.01). With regards to safety, first-line PD-1 inhibitors plus chemotherapy exhibited a greater likelihood of encountering TRAEs (RR=1.02, 95% CI: 1.00 to 1.04, P=0.03) and Grade≥3 TRAEs (RR=1.16, 95% Cl: 1.08 to 1.25, P<0.01) in comparison to chemotherapy. Conclusions Compared with chemotherapy alone, PD-1 inhibitors plus chemotherapy as first-line therapy provided improved OS, PFS, and ORR. Furthermore, the heightened efficacy of PD-1 inhibitors plus chemotherapy was accompanied by a rise in TRAEs and Grade≥3 TRAEs. Trial registration PROSPERO(CRD420251015248)
Keywords: gastric cancer, chemotherapy, PD-1 inhibitors, overall survival, Progression-free survival, Objective response rate, Treatment-related adverse events, Meta-analysis
Received: 21 Jun 2025; Accepted: 23 Oct 2025.
Copyright: © 2025 Tong, Zhou, Yin, Wang, Liang, Quan, Zhang, Wu and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yilun Wei, yilunwei202502@163.com
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