Bevacizumab to lose FDA approval for breast cancer treatment?

The news on bevacizumab is gaining traction again. Recently US Food and Drug Administration's (FDA) Oncology Advisory Panel recommended to withdraw approval for bevacizumab in the treatment of breast cancer. It may be noted that, in 2008, FDA went against the recommendation of its advisory panel and approved the drug for breast cancer treatment.

Bevacizumab which is marketed in the name Avastin by Genetech/Roche was initially approved as a combination drug to treat colon and non-small cell lung cancer and later to treat metastatic breast cancer. The FDA is now less convinced of its efficacy in treating advanced breast cancer. Studies following its initial approval showed only very short-term benefits, the progression-free survival improved only 24 days in one study and less than three months in the other. FDA is expected to take a final decision on the use of bevacizumab on September 17.

A major breast cancer research and service organization, Susan G Komen Foundation released a statement "Susan G. Komen for the Cure® and the Ovarian Cancer National Alliance are concerned about the potential impact on patients that could result from the Food and Drug Administration's Oncology Advisory Panel's recommendation to withdraw approval for bevacizumab. This agent, commonly known as Avastin, is a targeted therapy for patients with advanced breast cancer. We are concerned about patients who are presently receiving bevacizumab and the message that this decision sends about drug development in women with advanced breast cancer".

The side effects of bevacizumab treatment are due to the same effect of this antibody in slowing cancer growth. In the absence of functional VEGF there is heightened risk of bleeding as processes such as wound healing also require VEGF. Hypertension is another side effect observed. The issue has now become controversial. Susan Komen foundation has a case when they state that though the benefits of Avastin overall are modest for women with metastatic breast cancer, for some women, Avastin offers a greater benefit - but it is not yet known how to determine which patients will experience greater benefits.

Bevacizumab is an antibody to a protein critical in the formation of new blood vessels. Nutrition and oxygen are very important for the maintenance of existing tissues and growth of new tissues such as that occurring in cancer. If generation of new blood vessels is stopped, new tissue growth and cancerous growth of solid tumors can be halted. This is the scientific basis for the use of bevacizumab in cancer treatment, including breast cancer. A continuous supply of blood is needed for tumor cells to receive oxygen and nutrients for growth and survival. As a tumor grows, it signals the need for more blood by secreting growth factors such as VEGF triggering the formation of new blood vessels, a process called angiogenesis.

Bevacizumab binds to a protein called vascular endothelial growth factor (VEGF) and inhibits its binding to VEGF receptors on cell surface. VEGF binds to VEGF receptors to promote angiogenesis. When bevacizumab binds to VEGF, VEGF looses its ability to bind to VEGF receptors and angiogenesis is slowed down or prevented.

Bevacizumab is a monoclonal antibody, which means that all antibody molecules in bevacizumab preparation will have single specificity, specificity to bind on to the same site of VEGF. Monoclonal antibodies are usually raised in mouse and when found useful in human disease treatments these antibodies are chemically engineered to replace most of the mouse component with the human immunoglobulin fragment. This humanization procedure is essential to avoid mouse-antigen specific immune response in the recipient.

According to the National Cancer Institute website, Bevacizumab or Avastin is currently approved for treatment in metastatic renal cell carcinoma, second-line treatment of glioblastoma , metastatic HER2-negative breast cancer, first-line treatment of non-small cell lung cancer (NSCLC) , second-line treatment of metastatic colorectal cancer and first-line treatment of metastatic colorectal cancer.