%0 Journal Article
%T Bevacizumab and Breast Cancer: A Meta-Analysis of First-Line Phase III Studies and a Critical Reappraisal of Available Evidence
%A Jos¨¦ R. Rossari
%A Otto Metzger-Filho
%A Marianne Paesmans
%A Kamal S. Saini
%A Alessandra Gennari
%A Evandro de Azambuja
%A Martine Piccart-Gebhart
%J Journal of Oncology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/417673
%X Background. Randomized studies have shown different magnitude of bevacizumab benefit in the treatment of advanced breast cancer. Regulatory agencies have modified bevacizumab treatment indications across different regions. In this study, we perform a meta-analysis of phase III studies aiming to interrogate the magnitude of bevacizumab benefit for the treatment of first-line HER2-negative metastatic breast cancer (MBC). Methods. Data from studies E2100, AVADO and RIBBON-1 were used to calculate the benefit of bevacizumab in terms of tumor overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Combined statistical estimates of hazard ratios (HR) and odds ratios were calculated using fixed-effects or random-effects models. Results. A total of 2,695 patients were evaluated. Combining bevacizumab with different chemotherapy backbones resulted in a 30% risk reduction of PFS events (HR = 0.70; 95% confidence interval [CI], 0.57¨C0.86) and increased ORR (odds ratio 1.81; 95% CI, 1.53¨C2.14). No OS benefit could be demonstrated (HR = 0.95; 95% CI, 0.85¨C1.06). Bevacizumab significantly increased the incidence of adverse events such as proteinuria, hypertension and cardiovascular events. Conclusions. Bevacizumab combined with chemotherapy in the first-line treatment of MBC significantly improved ORR and PFS, but also increased grade 3-4 toxicities. No significant OS advantage was observed. 1. Introduction Vascular endothelial growth factor (VEGF) and its receptors are thought to play a pivotal role in tumor angiogenesis [1]. Bevacizumab is a humanized monoclonal antibody designed to block VEGF-A and has proved to be effective in colorectal cancer, nonsmall cell lung cancer, renal cell carcinoma, ovarian carcinoma, and glioblastoma multiforme [2¨C8]. In the field of breast cancer, bevacizumab has generated more controversies and discussions than any other targeted therapy. In February 2008, the FDA granted accelerated approval to bevacizumab in combination with paclitaxel for the first-line treatment of metastatic, HER2-negative metastatic breast cancer (MBC), based on promising results of the Eastern Cooperative Oncology Group (ECOG) 2100 trial. On July 20th 2010, the Oncologic Drugs Advisory Committee (ODAC) of the FDA¡¯s Center for Drug Evaluation and Research voted 12 to 1 against the use of bevacizumab in combination with chemotherapy for the first-line treatment of advanced breast cancer [9]. This was followed by a definitive announcement by the FDA revoking approval of bevacizumab for this indication [10].
%U http://www.hindawi.com/journals/jo/2012/417673/