TBCRC 022: Phase II trial of neratinib for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer and brain metastases (BCBM).

528 Background: Evidence-based treatments for metastatic, HER2+ breast cancer to the central nervous system (CNS) are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4 with promising activity in HER2+ disease. Preclinical evidence suggests it may cross the blood brain barrier. We evaluated neratinib in pts with HER2+ BCBM in a multicenter, phase II open label trial. We report the results of cohort 1 here. Methods: Pts with measurable BCMC (u003e/= 1 cm in longest dimension) who progressed after receipt of local CNS therapy were eligible. Pts received neratinib 240 mg orally once daily over 28 day cycles. Brain MRI and non-CNS imaging were obtained at baseline and every two cycles. Circulating tumor cell collections and neurocognitive evaluations were performed serially. The primary endpoint was composite CNS objective response rate (ORR). CNS ORR required all of the following: u003e/=50% reduction in volumetric sum of target CNS lesions, no progression of non-target lesions, no new lesions...