In early 2020, the US Food and Drug Administration (FDA) approved tucatinib, an oral tyrosine kinase inhibitor (TKI) of the protein ERBB2 (formerly HER2), in combination with trastuzumab and capecitabine for treatment of patients with locally advanced or metastatic breast cancer, including patients with brain metastases.1 The approval was based on HER2CLIMB (A Study of Tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Advanced HER2+ Breast Cancer),1,2 a randomized, double-blinded, placebo-controlled clinical trial that enrolled 612 patients and demonstrated statistically significant improvement in progression-free survival (PFS), overall survival (OS), and PFS in patients with brain metastases. Patients with active brain metastases have been historically excluded from clinical trials; however, HER2CLIMB enrolled patients with brain metastases, including those with progressing or untreated lesions.