A phase 2 single-arm study to assess clinical activity, efficacy and safety of enzalutamide (ENZA) with trastuzumab in HER2+ AR+ metastatic or locally advanced breast cancer.

TPS640 Background: Androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression have been found to correlate, with one series of breast carcinomas demonstrating AR expression in 77% of HER2+ tumors (Barton V et al. Mol Cancer Res. 2013;11:abstr A047). In vitro, ENZA inhibits proliferation of AR+/HER2+ cell lines and enhances the activity of trastuzumab. ENZA also inhibits proliferation of trastuzumab-resistant HER2+ cells (Micello D et al. Virchows Arch. 2010;457:467-476). Methods: Women with metastatic or locally advanced HER2+/ER-/PR- and AR+ (local or central) breast cancer will be enrolled in a phase 2 single-arm study (NCT02091960). Patients will receive daily ENZA (160 mg) continuously and trastuzumab (6 mg/kg) administered every 21 days until disease progression. Patients must have measurable disease per RECIST v1.1 and have received 1–4 prior lines of anti-HER2 therapy in the advanced/metastatic setting. Brain imaging is required to exclude patients with CNS metastases. Pa...