Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial

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.

Kohei Shitara, Yung-Jue Bang, Satoru Iwasa, Naotoshi Sugimoto, Min-Hee Ryu, Daisuke Sakai, Hyun Cheol Chung, Hisato Kawakami, Hiroshi Yabusaki, Yasuhiro Sakamoto, Tomohiro Nishina, Koichiro Inaki, Yusuke Kuwahara, Naoya Wada, Fumitaka Suto, Takeo Arita, Masahiro Sugihara, Zenta Tsuchihashi, Kaku Saito, Akihito Kojima, Kensei Yamaguchi