Protein levels may predict if patients with colorectal cancer patients benefit from bevacizumab

Patients with low levels of the protein VEGF165b who were treated with bevacizumab (Avastin) survived 3 months longer without their colorectal cancer progressing compared with patients not treated with bevacizumab. Bevacizumab increases survival in 10% to 15% of patients with colorectal cancer, but it has been impossible to predict who will benefit.

Bevacizumab targets and blocks the VEGF-A protein, whose two major forms are VEGF165 and VEGF165b. While VEGF165 helps cancers to grow new blood vessels, VEGF165b has the opposite effect and acts as a brake on the growth. Bevacizumab acts on both VEGF165 and VEGF165b. Treating those patients who have lower levels of VEGF165b with bevacizumab may block the blood vessel-promoting protein VEGF165, so that the cancer eventually starves.

This study examined the effect of bevacizumab on patients with different levels of VEGF165b and compared this with patients who did not receive bevacizumab.

Those patients with low levels of VEGF165b who received bevacizumab survived 3 months longer without the disease progressing than those who did not receive the drug. Those with higher levels of VEGF165b had no benefit from bevacizumab and had the same survival as those who did not receive the drug.

Professor David Bates, lead researcher from the University of Bristol School of Physiology and Pharmacology, said, “[Bevacizumab] has shown great potential for a minority of people with bowel cancer, but it's been impossible to predict who will benefit from the drug. Currently, [bevacizumab] is not approved by NICE for patients with advanced bowel cancer because they feel that the benefit to an unknown minority of patients does not justify the cost of treatment.” NICE is the National Institute for Health and Clinical Excellence in the United Kingdom, which uses the best available evidence to help health care professionals deliver the best possible care.

“We now need to look at cancer samples from a larger group of patients about to start taking [bevacizumab] and determine if the amount of VEGF165b can accurately identify those patients that will benefit and so potentially open a new treatment option for some people with advanced bowel cancer,” explained Bates.

Dr. Julie Sharp, senior science information manager at Cancer Research UK, said, “New targeted treatments can be hugely beneficial for certain patients, depending on the characteristics of their tumour. But, we don't always know who these patients are. This work takes researchers a step closer to developing a suitable test so doctors can give Avastin to those people it will really make a difference to.”

This study was published in Clinical Cancer Research (2012; doi:10.1158/1078-0432.CCR-12-2223).
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