Abstract
Abstract
Background
We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases.
Methods
We 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.
Results
Thirty-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.
Conclusions
The 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 registration
NCT01004172. Registered 28 October 2009.
Funder
American Society of Clinical Oncology Career Development Award
Breast Cancer Research Foundation
Dana-Farber Cancer Institute Women’s Cancers Program Executive Council Personalized Medicine Award
South-Eastern Norway Regional Health Authority
Norwegian Cancer Society
Genentech
Publisher
Springer Science and Business Media LLC