Anti-tumor efficacy of a bevacizumab preconditioning followed by etoposide and cisplatin regimen in human epidermal growth factor receptor-2-positive breast cancer brain metastasis refractory to whole brain radiotherapy

Abstract

Background: For human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC), treating brain metastasis (BM) remains challenging. We have previously demonstrated that administering bevacizumab 1 day before etoposide and cisplatin (BEEP) can significantly improve antitumor efficacy in cases of breast cancer with BM. Herein, we report the antimetastatic brain tumor efficacy of BEEP in an HER2-positive subpopulation. Materials and Methods: Thirty-five MBC patients with BM were enrolled from January 2011 to January 2013. BEEP was given in 21 day cycles: bevacizumab 15 mg/kg on day 1, etoposide 70 mg/m2/day from days 2 to 4, and cisplatin 70 mg/m2 on day 2. The primary endpoint was composite central nervous system (CNS) volumetric objective response rate (ORR). Anti-HER2 treatments were not permitted during the clinical trial. Results: A total of 23 patients were HER2-positive, 9 ER-positive, and 14 ER-negative. All had been exposed to trastuzumab; 11 (47.8%) had received lapatinib treatment, and 6 (26.1%) of them had received both lapatinib and capecitabine treatment. Of these, 16 patients (69.6%, 95% confidence interval [CI] 47.1–86.8) achieved CNS-ORR, including 7 (30.4%) with ≥80% and 9 (39.1%) with 50%–80% CNS volumetric reduction. A further 5 patients (21.7%) had 20%–50% CNS volumetric reduction. Median CNS-specific progression-free survival and overall survival were 7.4 (95% CI 5.8–9.0) and 11.8 (95% CI 8.7–14.9) months, respectively. Toxicities were tolerated with granulocyte-colony stimulating factor support. Conclusion: The BEEP regimen had a significant antitumor effect in cases of BM of HER2-positive breast cancer that progressed following whole brain radiotherapy.