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

Figures & data

Figure 1 Tumor cells secrete various isoforms of VEGF in a paracrine fashion. VEGFs stimulate the growth, division and permeability of vascular endothelial cells through interaction with cellular VEGF-receptors (VEGFR1 and VEGFR2). This process of neovascularization can be disrupted by the neutralizing humanized monoclonal antibody bevacizumab.

Table 1 Bevacizumab combinations with targeted agents currently under investigation

PI	Type of study	Regimen	Second target	Clinical trials. gov ID	Patient population
Genentech	Phase II	sunitinib + paclitaxel + Bevacizumab terminated due to toxicity)	VEGFR	NCT00434356	Metastatic breast cancer
Miller^Citation38	Phase II	bevacizumab + sorafenib (terminated after enrollment of 18 pts due to toxicities)	VEGFR	NCT00632541	Metastatic breast cancer
AMGEN	Randomized phase II	paclitaxel + bevacizumab ± AMG706	Multiple kinases, including VEGFR	NCT00356681	HER2-negative metastatic breast cancer
Yardly	Randomized phase II	paclitaxel + bevacizumab ± everolimus	mTOR kinase	NCT00915603	HER2-negative metastatic breast cancer
Dickler^Citation43	Phase II	erlotinib + bevacizumab (this combination had little efficacy^Citation43)	EGFR RTK	NCT00054132	Metastatic breast cancer
Erickson V	Non-comparative phase II	docetaxel + bevacizumab ± trastuzumab	HER2 RTK	NCT00364611	Her2-positive metastatic breast cancer
Glaxo	Phase II	lapatinib + bevacizumab	HER2 RTK	NCT00444535	Metastatic HER2 positive breast cancer
Genentech	Phase Ib	P13Kinase inhibitor GDC-0941 in combination with paclitaxel and bevacizumab	P13 kinase	NCT00960960	Metastatic breast cancer
Dickler^Citation43	Phase III	tamoxifen or letrozole + bevacizumab	Estrogen receptor	NCT00601900	Stage III or IV breast cancer

Notes: The studies that combine the anti-VEGF antibody bevacizumab with VEGFR-TKIs have been terminated due to toxicity. In addition, the combination of the EGFR-inhibitor erlotinib with bevacizumab has been reported and this combination had only limited therapeutic activity.

MillerKWangMGralowJPaclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancerN Engl J Med2007357262666267618160686

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DicklerMNRugoHSEberleCAA phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancerClin Cancer Res200814237878788319047117

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