Single-center experience with trastuzumab deruxtecan for leptomeningeal metastases of HER2-altered cancers

A retrospective review of patients of Stanford Medicine (Stanford, CA) characterized the activity of trastuzumab deruxtecan (T-DXd) for leptomeningeal metastases (LM) from a range of HER2-altered cancers. Among 18 patients, 6 had HER2+ breast cancer, 8 had HER2-low/negative breast cancer, 2 had HER2+ gastroesophageal cancer, and 2 had HER2-mutant non-small cell lung cancer. Partial response of LM to T-DXd was seen in 4 of 6 (67%) of patients with HER2+ breast cancer and 2 of 8 (25%) of patients with HER2-low/negative breast cancer, and 0 of 4 patients with HER2+ gastroesophageal cancer or HER2-mutant NSCLC. Median overall survival after initiatin T-DXd was 5.8 months. Survival after initiating T-DXd was numerically longer for HER2+ breast cancer patients compared with HER-low/negative breast and HER-altered non-breast cancer patients (13.9 months versus 5.2 months and 4.6 months, respectively). Landmark analysis showed that patients with radiologic response to T-DXd by 2.5 months had longer survival than non-responders (14.2 months versus 2.6 months; HR 0.18; p<0.05). The authors conclude that T-DXd induces LM responses in a subset of patients with HER2-altered cancers, and such responses may be associated with prologation of survival.