A new report indicates that the use of bevacizumab (Avastin) in the treatment of women with metastatic breast cancer slows the progression of the disease but has no impact on their overall survival, the length of time women live after receiving treatment, or on their quality of life.
The conclusion was reached by the Cochrane Breast Cancer Group, an international network, whose goal is to centralize data from clinical trials and help healthcare providers and researchers make well-informed decisions.
The group used data from seven trials that studied bevacizumab in combination with chemotherapy. Together, the studies involved 4,032 women, most of whom had metastatic breast cancer. Their results echo the 2011 findings that led the FDA to withdraw its approval for the medicine’s use in treating metastatic breast cancer.
Study Background and Goals
All cancers grow by creating new blood vessels through a process called angiogenesis. A key component of angiogenesis is vascular endothelial growth factor (VEGF), a protein that stimulates the growth of blood vessels. Prior clinical trials have shown that bevacizumab targets the VEGF protein and interferes with the growth of new blood vessels that are essential for tumor growth and spread, thereby slowing the progression of cancer.
The seven trials analyzed by Cochrane all aimed to explore whether adding bevacizumab to established chemotherapy treatments would impact women’s progression-free survival, the time between start of treatment and tumor progression.
History of Avastin
Bevacizumab is approved in the U.S. for certain types of colon, lung, brain and kidney cancer, and European officials kept its approval for metastatic breast cancer. Despite the side effects, the Cochrane analysis found that treatment-related deaths were lower in those treated with bevacizumab.
FDA had granted accelerated approval for bevacizumab in 2008 for treatment of metastatic breast cancer, based on its improvement in progression-free survival.
Bevacizumab stirred controversy when the FDA withdrew approval in November 2011 for its use in treating HER2 negative metastatic breast cancer, stating that the medicine was not safe and effective. The agency ruled that while bevacizumab did impact progression-free survival, the risk of life-threatening side effects was too high for a medicine that did not prolong life.
The ruling brought protest from many women already being treated with bevacizumab and their advocates, both in support of its medical potential and because revoked FDA approval impacts whether insurance companies cover the cost of treatment.
Researchers found that the combination of bevacizumab and chemotherapy improved the time to tumor growth by one to six months depending on the chemotherapy medicine used, but that it demonstrated no impact on overall survival or quality of life. Prompted by the results, they suggested that progression-free survival may not be an appropriate endpoint for clinical trials involving metastatic breast cancers. Endpoints are measures of whether the medicine works the way it should. In this case, the collaborative said the severity of side effects outweighed the benefits of the medicine, even though the progression-free survival endpoint was met in the original trials.
What This Means for You
The withdrawal of FDA approval for bevacizumab in metastatic breast cancer remains controversial. It is available through clinical trials and through off-label use as recommended by doctors. Many of these trials seek to identify traits or biomarkers of breast cancers that respond better to bevacizumab.
If you were treated with bevacizumab before the FDA revoked approval, your insurance company may still cover the cost if it is deemed medically necessary. Medicare announced in June 2011 its decision to cover the cost of bevacizumab even without FDA approval. Based on the clinical trial headed by Kathy Miller, MD, of paclitaxel with bevacizumab, which showed an improvement in progression-free survival by six months, treatment may be covered by some insurance companies. Contact your insurance or Medicare representative to find out if you are eligible.
Wagner AD, Thomssen C, Haerting J, Unverzagt S. Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD008941. DOI: 10.1002/14651858.CD008941.pub2