Offin M, Feldman D, Ni A, et al. - Among patients with human epidermal growth factor receptor 2 (HER2)-mutant (n = 98) lung cancers, researchers focused on the frequency and clinical course of brain metastases. This study included consecutive patients having HER2-mutant (n = 98), epidermal growth factor receptor (EGFR)–mutant (n = 200), and KRAS-mutant lung cancers (n = 200). For cases with HER2-mutant cancers, the estimated odds ratio for brain metastases at metastatic diagnosis was found to be similar to those for patients with KRAS mutations but was lower than those estimated for patients with EGFR mutations. The development of brain metastases on treatment was more in patients with lung cancer and HER2 mutations compared with patients with KRAS mutations, and the former group trended more than patients with EGFR mutations. Compared with patients with EGFR-mutant lung cancers, shorter median overall survival (OS) was reported in patients with HER2-mutant or KRAS-mutant lung cancers. The occurrence of brain metastases was reported in 47% of patients with HER2-mutant lung cancers and was associated with shorter OS (HR, 2.7; p < .001). The necessity to develop HER2-targeted agents with central nervous system activity was highlighted.