Retrospective study of HER2 loss after trastuzumab deruxtecan for metastatic breast cancer

Trastuzumab deruxtecan (T-DXd) is approved for treating metastatic breast cancer (mBC) that is HER2 positive or HER2-low, as well as HER2-potive gastric cancer, HER2-mutant lung cancer, and HER2-overexpressing solid tumors. A retrospective study at MD Anderson Cancer Center (Houston, TX) evaluated changes in HER2 status following T-DXd therapy. The study included 41 patients treated with T-DXd for mBC, with available paired pre- en post-treatment biopsies for assessing HER2 status using immunohistochemistry. Following T-DXd treatment, HER2 loss was observed in 11 patients (32.4% of 34 patients with pre-treatment HER2 expression). Another 10 patients (29.4%) had a decrease in HER2 score after T-DXd. The authors conclude that HER2 loss and decrease in HER2 expression are common in mBC patients receiving T-DXd. Reevaluation of HER2 status following T-DXd treatment should be considered prior to alternate HER2-targeted therapies.