Evidence for the role of bevacizumab in the treatment of advanced metastatic breast cancer: a review

Abstract

Angiogenesis inhibitors may provide a new approach to the treatment of metastatic breast cancer. Bevacizumab is a monoclonal antibody against pathologic angiogenesis. A pivotal study (ECOG 2100) showed that bevacizumab in combination with paclitaxel increased progression-free survival for patients with metastatic breast cancer by 6 months. Subsequently, several clinical trials have shown that the combination of bevacizumab with a taxane can improve disease-free survival but does not prolong overall survival. While generally well tolerated, bevacizumab is potentially toxic for some patients who develop hypertension, proteinuria, bleeding, impaired wound healing, bowel perforation or thromboembolic events. Here, we review the current evidence for the use of bevacizumab in breast cancer and ongoing studies that address the questions of how to optimize regimens and schedules for the use of anti-angiogenic agents and the identification of those patients who would benefit the most from treatment with regimens that include antiangiogenic therapy.

Integrative In Vivo Drug Testing Using Gene Expression Signature and Patient-Derived Xenografts from Treatment-Refractory HER2 Positive and Triple-Negative Subtypes of Breast Cancer

“…On the basis of previous studies that have targeted VEGFA in breast cancer [14,15,16,17], we tested the tumor-suppressive effects of bevacizumab, a humanized Vascular Endothelial Growth Factor A (VEGFA) antagonist and docetaxel, which was chosen with the consideration of treatment history on PDX models derived from PT12 (Figure 3). The combination of bevacizumab and docetaxel were widely used in metastatic breast cancer treatment [18]. Treatment with docetaxel or bevacizumab individually for 28 days significantly decreased volumes of PDX model tumors from PT12; drug treatment was well tolerated as indicated by the lack of significant body weight loss ( p ≤ 0.05 for control vs. docetaxel and control vs. bevacizumab) (Figure 3C,D and Figure S1B).…”

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study

“…Therapeutic disruption of tumor neo-vascularization can be achieved by using bevacizumab, which recognizes human VEGF, thereby eliminating the ligands required for VEGF-R activation and the mitogenic and permeability-enhancing stimuli necessary for neo-vascularization. Given that bevacizumab is a monoclonal antibody, it is distributed to highly perfused areas with a linear kinetic profile [ 11 , 35 ]. The increased microvascular permeability induced by HT, that facilitates the bevacizumab distribution in cancer tissues emphasizing its therapeutic efficacy, represents just one of the potential synergic antiangiogenic and proapoptotic effects for combining bevacizumab-based chemotherapy and HT.…”

“…Clinically, bevacizumab has been investigated in combination with a range of chemotherapeutic agents for the treatment of different metastatic cancer; its efficacy was tested in metastatic colorectal cancer, in combination with irinotecan and 5-fluorouracil/leucovorin [ 5 , 6 ], and in non-small-cell lung cancer, in combination with paclitaxel and carboplatin [ 7 , 8 ]. In addition to metastatic lung and colorectal cancer, bevacizumab was recently also approved for the treatment of metastatic renal cell, ovarian, and breast cancer [ 9 , 10 , 11 ]. However, the outcome resulting from anti-angiogenic therapy, is variable [ 6 , 8 , 10 , 11 , 12 , 13 ].…”

“…In addition to metastatic lung and colorectal cancer, bevacizumab was recently also approved for the treatment of metastatic renal cell, ovarian, and breast cancer [ 9 , 10 , 11 ]. However, the outcome resulting from anti-angiogenic therapy, is variable [ 6 , 8 , 10 , 11 , 12 , 13 ]. While the approvals in lung and colorectal cancer were based on an improved overall survival (OS) with bevacizumab [ 6 , 8 ], the approvals in metastatic renal, ovarian, and breast cancer were based on an improvement in progression-free survival without prolonging OS.…”

Active Roles of Tumor Stroma in Breast Cancer Metastasis

“…Unlike trastuzumab which is a HER-2-targeted antibody, avastin delayed tumor progression with no improvement in overall survival. This was accompanied by adverse side effects including hypertension, neuropathy, and infection [ 95 ]. Recently, a variety of studies have been conducted to target the tumor microenvironment.…”