Lapatinib plus Capecitabine for Brain Metastases in Patients with Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Review of the Anatolian Society of Medical Oncology (ASMO) Experience

Approximately 20–25% of all breast cancers are human epidermal growth factor receptor 2-positive (HER2+) and have historically been associated with poorer disease-free survival (DFS) and overall survival (OS) [1]. For patients with HER2+ metastatic breast cancer (MBC), the use of humanized monoclonal antibody trastuzumab (Herceptin® , Genentech, San Francisco, CA, USA) in combination with chemotherapy has become the standard of care. Approximately one third of patients with MBC treated with trastuzumab-containing therapy develop brain metastases (BMs) [2, 3]. Concerns have also been raised about high rates of BMs following systemic response to trastuzumab. Trastuzumab does not fully cross the blood-brain barrier, making the brain a ‘sanctuary’ site [4, 5]. Recently, a literature-based meta-analysis of randomized phase III clinical trials including trastuzumab as adjuvant therapy for early-stage breast cancer demonstrated that patients receiving trastuzumab therapy had a significantly higher risk for developing central nervous system (CNS) metastases compared to the patients treated with non-trastuzumab-containing regimens (relative risk 1.57, 95% confidence interval (Cl) 1.03–2.37) [6]. Increased incidence of BMs in MBC limits the benefits of new systemic treatment modalities. Current treatments for BMs are palliative, including stereotactic radio surgery or whole-brain radiotherapy (WBRT). Treatment options for CNS metastases from HER2+ MBC remain limited, while only a few prospective trials have been conducted [7, 8]. Lapatinib (Tykerb® , GlaxoSmithKline, Philadelphia, PA, USA) was approved in combination with capecitabine in patients with HER2+ MBC after progression under trastuzumab treatment based on a pivotal phase III study [9]. Compared to trastuzumab, lapatinib shows restricted but improved brain uptake by reaching levels up to one-quarter of those in plasma [10]. Lapatinib may reduce the risk of disease pro gression in the CNS based on the results from exploratory analyses performed from the pivotal phase III trial [11]. In this regard, the present study was undertaken to evaluate the clinical efficacy and adverse effect profile of lapatinib + capecitabine (LC) combination therapy in patients with HER2+ MBC and BMs, who progressed after trastuzu