Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases

Brain metastases of breast cancer (BCBMs) can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from pivotal clinical trials, the central nervous system (CNS) activity of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is not well characterized. A multicenter study in the USA found CNS activity of T-DXd in HER2-positive and HER2-low PDX models of BCBMs. There was preliminary evidence of clinical activity of T-DXd in a multi-institution case series of patients with predominantly HER2-positive BCBMs.