Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases

Breast Cancer Res. 2020 Nov 30;22(1):131. doi: 10.1186/s13058-020-01372-w.


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.

Keywords: Bevacizumab; Brain metastases; Breast cancer.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary
  • Breast / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carboplatin / administration & dosage*
  • Carboplatin / adverse effects
  • Female
  • Genotyping Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Progression-Free Survival
  • Trastuzumab / administration & dosage
  • Trastuzumab / adverse effects
  • Vascular Endothelial Growth Factor A / genetics


  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Carboplatin
  • Trastuzumab

Associated data