Abstract
BackgroundWe aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases.MethodsWe enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24–96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes.ResultsThirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46–78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1–2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed.ConclusionsThe combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation.Trial registrationNCT01004172. Registered 28 October 2009.
Highlights
Up to half of patients with human epidermal growth factor receptor 2 (HER2)-positive or triple-negative metastatic breast cancer, and 10–15% of patients with estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer, will develop brain metastases [1, 2]
At the time the study was designed, improvements in the objective response rate (ORR) and progression-free survival (PFS) had been reported among patients with HER2-negative metastatic breast cancer when bevacizumab was added to chemotherapy, and dual antibody blockade with bevacizumab and trastuzumab was shown to produce objective responses in HER2-positive disease [6, 7]
The combination of cisplatin and etoposide has been reported in a small study to lead to a central nervous system (CNS) ORR of 38% in breast cancer patients, albeit in a patient population that was less refractory than typical contemporary patients [9]
Summary
Up to half of patients with human epidermal growth factor receptor 2 (HER2)-positive or triple-negative metastatic breast cancer, and 10–15% of patients with estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer, will develop brain metastases [1, 2]. The management of patients with brain metastases is a continuing challenge. Preclinical data suggest that vascular endothelial growth factor (VEGF) promotes the growth of breast cancer brain metastases and that treatment with antiangiogenic agents results in tumor regression [4, 5]. At the time the study was designed, improvements in the objective response rate (ORR) and progression-free survival (PFS) had been reported among patients with HER2-negative metastatic breast cancer when bevacizumab was added to chemotherapy, and dual antibody blockade with bevacizumab and trastuzumab was shown to produce objective responses in HER2-positive disease [6, 7]. We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases
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