SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1668511
Efficacy and safety of antibody-drug conjugates for HER2-expressing advanced gastric and gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis
Provisionally accepted
- 1Liaoning Cancer Hospital, China Medical University, Shenyang, China
- 2Liaoning Cancer Hospital and Institute, Shenyang, China
- 3Jiangsu Hengrui Pharmaceuticals Co Ltd, Lianyungang, China
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Background Antibody-drug conjugates (ADCs) represent a promising therapeutic modality for gastric cancer. Given the highly heterogeneous nature of this malignancy, the efficacy and safety profile of ADC treatment warrant comprehensive evaluation. Methods A systematic search of online databases identified prospective trials published through June 2025. Pooled estimates for OS, PFS, ORR, DCR, and TRAEs were derived using a random-effects model. Subgroup analyses were performed, stratified according to HER2 status, primary tumor location, line of therapy, and use of combination treatment. Results A total of 1779 patients from 13 prospective trials (18 reports) were included. The pooled ORR was 67% (95% CI: 53-82%) for first-line ADC therapy, 40% (95% CI: 29-51%) for second-line regimens, and 27% (95% CI: 16-38%) for third-line regimens. In second-line or later therapy, HER2-positive patients achieved a superior ORR relative to HER2-low subgroups (39%, 30-47% vs. 25%, 11-39%). The overall pooled median OS was 11.95 months (95% CI: 9.93-13.96), with a median PFS of 4.94 months (95% CI: 3.92-5.96). Stratification by line of therapy revealed a median OS of 19.67 months (95% CI: 15.79-23.55) for first-line versus 11.65 months (8.09-15.22) for second-line and 9.37 months (7.38-11.37) for third-line, with corresponding median PFS of 10.57 months (6.37-14.77) vs. 4.13 months (2.43-5.83) and 4.50 months (3.51-5.50) respectively. TRAEs occurred in 98% (95% CI: 96-100%) of patients (any-grade), with grade 3-5 events in 60% (52-69%). Conclusions This meta-analysis establishes ADCs as a promising therapeutic approach for advanced gastric or gastroesophageal junction cancer (GC/GEJC), demonstrating efficacy in both HER2-positive and HER2-low patient populations.
Keywords: gastric cancer, Antibody-drug conjugates, Gastroesophageal junction adenocarcinoma, Meta-analysis, HER2-expressing
Received: 18 Jul 2025; Accepted: 08 Sep 2025.
Copyright: © 2025 Huang, Feilong, Li and Ke. 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: Danxue Huang, Liaoning Cancer Hospital, China Medical University, Shenyang, China
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