Trastuzumab-capecitabine with tucatinib or placebo for pretreated HER2-positive metastatic breast cancer with brain metastases

Up to 50% of patients with HER2-positive metastatic breast cancer (MBC) will develop brain metastases (BMs), which is associated with poor prognosis. A subgroup analysis of the HER2CLIMB randomized trial compared tucatinib-trastuzumab-capecitabine versus placebo-trastuzumab-capecitabine for heavily pretreated HER2-positive MBC with BMs. At median follow-up of 29.6 months, median overall survival was 21.6 months in the tucatinib-combination group versus 12.5 months in the placebo-combination group. The tucatinib-combination group also had better CNS-progression-free survival, intracranial objective response rate, and duration of intracranial response. Risk of developing new brain lesions as the site of first progression was lower in the tucatinib-combination group (visual abstract).