SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1684873
Antibody-Drug Conjugates in HER2-Positive Advanced or Metastatic Gastric Cancer: A Systematic Review and Meta-Analysis
Provisionally accepted
- 1Zhejiang Chinese Medical University First Clinical Medical College, Hangzhou, China
- 2Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China
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Background: Antibody-drug conjugates (ADCs) are an emerging therapy for HER2-positive advanced gastric cancer (AGC), yet their comparative efficacy and safety remain unclear. This systematic review and meta-analysis aimed to evaluate the clinical outcomes of different ADCs in this patient population. Methods: A systematic search of PubMed, Embase, Cochrane, and Scopus databases was performed to identify relevant studies. The primary endpoint was the pooled overall response rate (ORR), analyzed using a random-effects model. Safety, subgroup analyses, and publication bias were also assessed. Results: Twelve studies comprising 1041 patients were included. The pooled ORR across all ADCs was 33.4% (95% CI, 26.3%–41.3%). Efficacy varied substantially among agents: trastuzumab deruxtecan (T-DXd) and DP303c demonstrated the highest ORRs (42.5% and 42.9%, respectively), whereas others, such as Trastuzumab emtansine (T-DM1), showed lower efficacy (20.6%). ORR was not significantly affected by prior treatment lines (P=0.6559) or cohort type (P=0.7185). The most common adverse events included nausea (47.7%), with grade ≥3 anaemia (21.1%) and neutropenia (15.1%) being the most frequent severe toxicities. Conclusions: The efficacy of ADCs in HER2-positive AGC is highly variable. T-DXd and DP303c appear to be the most active agents, underscoring the critical importance of specific drug selection. Managing toxicities such as anaemia and neutropenia is essential for optimizing treatment.
Keywords: Antibody-drug conjugate, HER2-positive, Advanced gastric cancer, Metastatic gastric cancer, Subsequent-line treatments, Meta-analysis, efficacy, Safety
Received: 13 Aug 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 Li, Chen, Chai and Qiu. 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: Shengliang Qiu, shengliang.qiu@zcmu.edu.cn
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