Phase 2 study of trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases

Trastuzumab deruxtecan (TD) is an antibody-drug conjugate with high extracranial activity in HER2-positive metastatic breast cancer (MBC). The phase 2 TUXEDO-1 study at the Medical University of Vienna (Austria) evaluated TD for HER2-positive MBC with brain metastases (BMs). The study included 14 women and 1 man; 60% had BMs progressing after previous local therapy, and 60% had received previous ado-trastuzumab emtansine. Two patients (13.3%) had a complete intracranial response, nine (60%) had a partial intracranial response, and three (20%) had stable disease as best intracranial response, with a best overall intracranial response rate of 73.3% (95% CI 48.1-89.1), meeting the predefined primary outcome. No new safety signals were observed, and global quality-of-life and cognitive function were maintained over the treatment duration. The authors conclude that TD showed a high intracranial response rate in patients with active BMs from HER2-positive MBC and should be considered as a treatment option in this setting.