Abstract
SummaryBased on a strong rationale for anti-VEGF (vascular endothelial growth factor) treatment in breast cancer and promising preclinical data, great hopes have been placed on the anti-VEGF antibody bevacizumab. Clinical trials, however, reported conflicting results. In metastatic human epidermal growth factor receptor 2(HER2)-negative breast cancer, the addition of bevacizumab to standard chemotherapy improved consistently progression-free survival (PFS), however, without effect on overall survival (OS). In early breast cancer bevacizumab increased the pathologic complete response rate (pCR) after neoadjuvant therapy, but adjuvant trials did not demonstrate an effect on long-term survival. Unfortunately, despite extensive research, there is still no biomarker for bevacizumab efficacy available, making patient selection difficult. This review summarizes all phase III trials investigating efficacy and toxicity of bevacizumab in early, locally advanced and metastatic breast cancer. It recapitulates the main toxicities, gives an overview on biomarker studies and discusses the role and future aspects of antiangiogenic therapy in breast cancer.
Highlights
There is a strong rationale for the usage of antiangiogenic therapies in early, locally advanced and metastatic breast cancer
Four prospective phase III trials investigated the efficacy and tolerability of bevacizumab in combination with chemotherapy as first-line therapy in human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer (Table 1). The approval for this indication was based on the results of the E2100 trial, where the combination of bevacizumab 10 mg/kg on days 1 and 15 and paclitaxel 90 mg/m2 on days 1, 8 and 15 every 4 weeks showed a significant and clinically meaningful improvement in progression-free survival (PFS) compared to paclitaxel alone (11.8 months vs. 5.9 months; hazard ratio [HR] 0.60; P < 0.001) [7]
In the ARTEMIS trial, patients achieving a pathologic complete response rate (pCR) in the bevacizumab group showed no longer disease-free survival (DFS) suggesting a lack of activity against micrometastases
Summary
Received: 12 September 2017 / Accepted: 23 October 2017 / Published online: 6 November 2017. In metastatic human epidermal growth factor receptor 2(HER2)-negative breast cancer, the addition of bevacizumab to standard chemotherapy improved consistently progression-free survival (PFS), without effect on overall survival (OS). In early breast cancer bevacizumab increased the pathologic complete response rate (pCR) after neoadjuvant therapy, but adjuvant trials did not demonstrate an effect on long-term survival. This review summarizes all phase III trials investigating efficacy and toxicity of bevacizumab in early, locally advanced and metastatic breast cancer. Gampenrieder; Collection and assembly of data: Simon P. Gampenrieder and Theresa Westphal; Data analysis and interpretation: All authors; Manuscript writing: Simon P. MD Laboratory of Immunological and Molecular Cancer Research and Center for Clinical Cancer and Immunology Trials, Salzburg Cancer Research Institute, Salzburg, Austria. Cancer Cluster Salzburg, Salzburg, Austria toxicities, gives an overview on biomarker studies and discusses the role and future aspects of antiangiogenic therapy in breast cancer
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