Efficacy and safety of antibody-drug conjugates for HER2-expressing advanced gastric and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis.
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引用次数: 0
Abstract
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%).
Conclusion: 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.
期刊介绍：
Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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