A Phase Ii Study Of Cabozantinib (Cabo) Alone Or In Combination With Trastuzumab (T) In Patients (Pts) With Breast Cancer Brain Metastases (Bcbm)

1026Background: BCBM rely on VEGF pathway activation for angiogenesis and dissemination. Activation of MET leads to tumor invasion and resistance to anti-VEGF therapy. The aim of this study was to analyze the efficacy and tolerability of cabo —a small molecule inhibitor of MET and VEGFR2— alone or with T in BCBM pts. Methods: This is a single-arm, two-stage phase II study. Eligible pts had new or progressive measurable BCBM. The study included 3 cohorts: Cohort 1 (HER2+), Cohort 2 (HR+ HER2-) and Cohort 3 (triple negative). Pts received cabo 60 mg daily on a 21-day cycle. Cohort 1 also received standard T every 3 weeks. Pts had restaging scans every 6 weeks for 6 cycles, then every 9 weeks; a research brain MRI was performed at baseline and after 1 cycle. Primary objective was CNS objective response rate (ORR) by RECIST 1.1 in Cohort 1. Target sample size for Cohort 1 was 21 pts; if ≥ 3 pts had CNS ORR the null rate (5%) would be rejected in favor of a 30% rate of activity. Secondary objectives were CNS O...