ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1564604
First-line immune checkpoint inhibitors with chemotherapy in advanced gastric and gastroesophageal adenocarcinoma: A meta-analysis of phase 3 trials
Provisionally accepted
- 1Sun Yat-sen University, Guangzhou, Guangdong Province, China
- 2Guangxi Medical University, Nanning, China
- 3China Pharmaceutical University, Nanjing, Jiangsu Province, China
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The integration of immune checkpoint inhibitors (ICIs) with chemotherapy (CT) regimens has become a critical focus of clinical investigation in the management of advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma over the past several years. Recent phase 3 trials have yielded diverse outcomes, sparking significant debate within the oncological community.In response to these disparate findings, we conducted a meta-analysis to evaluate the therapeutic efficacy and safety profile of this strategy.Methods: A literature search on PubMed and in major conference proceedings was carried out through December 15, 2024. For efficacy, summary hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), odds ratios (ORs) for the objective response rate (ORR) were calculated; for safety, relative risks (RRs) for adverse events (AEs) were assessed.Results: Nine phase 3 clinical trials, including KEYNOTE-062, CheckMate 649, ATTRACTION-4, ORIENT-16, GEMSTONE-303, KEYNOTE-811, KEYNOTE-859, RATIONALE-305, and COMPASSION-15, which involved a total of 7,825 patients, were analyzed. The addition of ICIs to CT was associated with better PFS (HR, 0.71; 95% CI, 0.65-0.79), OS (HR, 0.79; 95% CI, 0.75-0.83), and a higher ORR (OR, 1.57; 95% CI, 1.43-1.72) compared with CT standalone treatment. However, this combination therapy increased the risk of grade 3-5 AEs (RR, 1.15; 95% CI, 1.09-1.22) and severe AEs (RR, 1.44; 95% CI, 1.21-1.70).For patients with advanced G/GEJ adenocarcinoma, the addition of ICIs to CT regimens as a first-line treatment offers superior efficacy compared to CT alone, though it comes with an increased risk of toxicity. In the context where multiple strategies are accessible, the pharmacological safety profile can guide practitioners in identifying the most suitable intervention for patients with a higher likelihood of deriving benefits from specific treatment strategies.
Keywords: immune checkpoint inhibitors, chemotherapy, gastric cancer, Gastroesophageal junction adenocarcinoma, Meta-analysis
Received: 21 Jan 2025; Accepted: 14 Apr 2025.
Copyright: © 2025 Lin, Liao and Shen. 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: Jinhai Shen, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, China
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