Phase I study of lapatinib (L) and temozolomide (T) combination for the treatment of progressive brain metastases (BM) in HER2-positive metastatic breast cancer patients (Pts) (LAPTEM, LAP 111172)

570 Background: Previous trials have suggested the efficacy of either L or T for the treatment of brain metastases. This study was designed to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of L + T in pts with BM from HER2+ metastatic breast cancer. Methods: Eligible pts had HER2+ breast cancer and recurrent or progressive BM. Previous chemotherapy, trastuzumab, L and brain RT/surgery/radiosurgery were allowed. Measurable brain disease was required (> 5mm by volumetric MRI). Adequate cardiac, renal, bone marrow and hepatic functions prior to study entry were required. Patients were enrolled in one of the cohorts and treated as per the table. The primary endpoint was the determination of the MTD, defined as the dose level below that dose in which ≥ 2/3 or ≥ 2/6 pts experience DLT in the first cycle. Volumetric brain MRI was performed at baseline and every two cycles during therapy. Secondary endpoints included objective response, clinical benefit and duration of response. Th...