Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer

503 Background: One-third of women with HER2+ metastatic breast cancer develop central nervous system (CNS) metastases. This study evaluated the safety and efficacy of lapatinib, an oral inhibitor of EGFR and HER2, in patients with HER2+ brain metastases. Methods: Eligible patients (pts) had HER2+ breast cancer, new or progressive brain metastases, and at least one measurable (LD ≥1.0cm) lesion. Pts received lapatinib 750 mg PO BID. Tumor response was assessed by MRI every 8 wks. FDG-PET scans were performed at baseline, and repeated at wks 1 and 8. The primary endpoint was objective response (CR+PR) in the brain by RECIST. Secondary endpoints included safety, quality-of-life (QOL), and PET changes. Sample size was calculated using a 2-stage design to distinguish objective response of 5% (H0) vs 20% (HA); ≥ 4 objective responses were required to reject the null hypothesis. Results: 39 pts were enrolled, mean age 52 yrs (range 31–76). All pts developed CNS disease on trastuzumab; 38 progressed after prior ...