Antibody-drug conjugates in HER2-positive advanced or metastatic gastric cancer: a systematic review and meta-analysis.

[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 anemia (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 anemia and neutropenia is essential for optimizing treatment.

[SYSTEMATIC REVIEW REGISTRATION] https://www.crd.york.ac.uk/PROSPERO/view/CRD420250653886, identifier PROSPERO CRD420250653886.