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

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.

Breast Cancer Subtypes and Mortality of Breast Cancer Patients With Brain Metastasis at Diagnosis: A Population-Based Study

“…9,10 Although the blood-brain barrier limits delivery of systemic treatments, the combination of chemotherapy and anti-angiogenic drugs can produce a high objective response rate to metastatic brain tumors in BC patients. 11 Furthermore, retrospective cohort studies have demonstrated the survival benefit in metastatic breast cancer patients via the surgical removal of primary tumors and systemic treatments. 12,13 Although previous studies have analyzed the relationship between newly diagnosed BM patients and subtypes, no further analysis of prognostic factors of breast cancer has been performed.…”

Breast Cancer Brain Metastasis—Overview of Disease State, Treatment Options and Future Perspectives

“…Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. In a phase II trial evaluating the efficacy of carboplatin and bevacizumab for patients with BCBM (29 HER2-positive and 9 HER2-negative), the objective response rate was 63% (95% CI, 46–78%), the median PFS was 5.62 months, and the median OS was 14.10 months [ 83 ]. Furthermore, a phase II trial (NCT01281696) is investigating the efficacy of bevacizumab, cisplatin, and etoposide in patients with CNS metastasis.…”

TAMs in Brain Metastasis: Molecular Signatures in Mouse and Man

“…While double inhibition of VEGF and ANG-2 reduced BrM burden in preclinical models of breast-to-brain metastasis (76), VEGFA inhibition can induce long-term dormancy in lung-to-brain metastasis (90). For breast-to-brain metastasis patients, combination of VEGFA inhibition with bevacizumab in combination with carboplatin resulted in a high rate of durable responses (77). Moreover, VEGFA inhibition resulted in a 25% disease response rate in 80% of solid cancer patients with current brain metastasis that failed whole-brain radiotherapy (78).…”