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

• DOI: 10.1186/s13058-020-01372-w
• Publication Date: 2020-11-30T11:03:07Z
• Authors: Jose Pablo Leone; Kyrre E. Emblem; Michelle Weitz; Rebecca S. Gelman; Bryan P. Schneider; Rachel A. Freedman; Jerry Younger; Marco C. Pinho; A. Gregory Sorensen; Elizabeth R. Gers...; Gordon Harris; Ian E. Krop; Daniel Morganstern; Jessica Sohl; Jiani Hu; Elizabeth Kasparian; Eric P. Winer; Nancy U. Lin
• Keywords: Adult; Vascular Endothelial Growth Factor A; Genotyping Techniques; Breast Neoplasms; Kaplan-Meier Estimate; Polymorphism, Single Nucleotide; Carboplatin; 03 medical and health sciences; Breast cancer; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Humans; Breast; RC254-282; Brain Neoplasms; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Brain; Brain metastases; Middle Aged; Trastuzumab; Magnetic Resonance Imaging; Progression-Free Survival; 3. Good health; Bevacizumab; Female; Research Article

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.