What type of study is this?

This is a Meta-Analysis study (also classified as: Systematic Review).

September 18, 2025Open Access

Efficacy and safety of antibody-drug conjugates for HER2-expressing advanced gastric and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis

Key Points

Pooled overall response rate for first-line ADC therapy was 67%, highlighting its efficacy.
Adverse events occurred in 98% of patients, with significant grade 3–5 events in 60% of cases, suggesting the need for careful monitoring.
Patients receiving first-line therapy achieved a median overall survival of 19.67 months, underscoring the importance of treatment sequencing.
Subgroup analyses revealed higher efficacy in HER2-positive patients compared to HER2-low, indicating the value of HER2 status in treatment decisions.

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. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251066208 , identifier CRD420251066208.

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