Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory analyses assessed baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, investigating mechanisms of resistance to T-DXd. Baseline HER2 biomarkers correlated with objective response rate (ORR) in the HER2+ cohort. Other key driver gene amplifications (MET, EGFR, FGFR2) were associated with numerically lower ORR. ORR was consistent regardless of immunohistochemistry sample collection timing. Further investigations are needed.
