Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases

BACKGROUND: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit. METHODS: Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy. RESULTS: Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012). INTERPRETATION: This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ⩾70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.