Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer.

In non-small-cell lung cancer (NSCLC), activating human epidermal growth factor receptor 2 (HER2) mutations are found in a small subset of patients and are associated with a higher incidence of brain metastases (BMETSs), conferring poor survival outcomes. Trastuzumab deruxtecan (T-DXd) was recently approved as a second-line agent for use in patients with previously treated, unresectable, or metastatic HER2-mutated NSCLC. We present a case of HER2-mutated NSCLC with BMETS, treated with T-DXd to defer whole-brain radiotherapy (WBRT) because of the concern of long-term neurotoxicity. He initially also received bevacizumab to address the cerebral edema, which allowed stopping corticosteroids. After the first two doses, the patient had remarkable clinical and imaging (brain and systemic) responses without progression after more than 1 year of treatment. T-DXd may be an effective and durable therapy for patients with HER2-mutated NSCLC with brain metastases in situations where intracranial disease would otherwise warrant WBRT. Clinical trials are needed to understand the efficacy and durability of T-DXd in NSCLC with BMETS and the optimal sequence of available therapies.