Murthy RK, Loi S, Okines A, et al. - Since there are limited treatment choices for patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer who experience disease progression following therapy with multiple HER2-targeted agents, researchers assessed progression-free survival among the first 480 patients with HER2-positive metastatic breast cancer earlier managed with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, who were randomized to either tucatinib or placebo, in combination with trastuzumab and capecitabine. They also evaluated secondary endpoints in the overall population (612 patients), including overall survival, progression-free survival in patients with brain metastases, confirmed objective response rate, and safety. Findings revealed better progression-free survival and overall survival outcomes in relation to adding tucatinib to trastuzumab and capecitabine vs adding placebo in the treatment of heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases. However, tucatinib was associated with higher risks of diarrhea and elevated aminotransferase levels.