Controversial Avastin Spit and Ship Study to Help Triple Negative Breast Cancer Patients
Undeterred by the U.S. Food and Drug Administration (FDA) removal of Avastin for breast cancer, makers of the drug are now seeking breast cancer patients who have previously used Avastin to provide saliva samples in a spit and ship study titled “The InVite Study” to determine if there is a subset of women with breast cancer—such as those diagnosed with triple negative breast cancer—who may still benefit from Avastin.
Avastin holds the distinction of being the first FDA-approved therapy designed to inhibit angiogenesis, the process by which new blood vessels develop and nourish a growing tumor. The proposed mechanism of action of Avastin is that it targets and inhibits a protein called "vascular endothelial growth factor" (VEGF) that stimulates new blood vessel formation. Studies have shown that the anti-VEGF actions of Avastin are believed to cause:
• Regression of existing microvessels — helps arrest tumor growth and reduce tumor size
• "Normalization" of surviving mature vasculature — makes the tumor vasculature more conducive to effective anti-cancer therapy
• Inhibition of vessel growth and neovascularization (e.g., the sprouting of new micro-vasculature from existing vessels)
Avastin’s use as a drug for treating metastatic breast cancer was approved in February 2008 under the FDA’s accelerated approval program. The accelerated approval program allows drugs to be approved based on early, initial data that does not sufficiently qualify full approval in order to provide earlier patient access to promising new drugs to treat serious or life-threatening conditions that would otherwise lead to death before full approval can be obtained for a promising therapy.
While in the early approval phase, clinical trials are conducted to determine whether or not the drug is satisfactorily safe and effective. If the clinical trials do not justify the continued approval of the drug or a specific drug indication, the agency may revoke its approval.
In the case of Avastin during its accelerated approval, its maker Genentech, performed additional clinical studies and submitted the results to the FDA. However, the FDA determined that the data from the clinical studies showed only a small effect on tumor growth without evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone. Their determination was that the benefits of taking Avastin were outweighed by the risks of side effects and therefore announced that Avastin’s initial approval would be revoked as a drug for the treatment of breast cancer.
In their announcement the FDA warned that taking Avastin may result in:
• Gastrointestinal (GI) perforation: Avastin can result in the development of a potentially serious and sometimes fatal side effect called GI perforation, which is the development of a hole in the stomach, small intestine or large intestine. Symptoms may include abdominal pain, nausea, vomiting, constipation, and fever. Patients must stop Avastin for at least 28 days before voluntary surgery.
• Surgery and wound healing problems: Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality.
• Severe bleeding: Treatment with Avastin can result in serious and sometimes fatal bleeding. This includes coughing up blood, bleeding in the stomach, vomiting blood, bleeding in the brain, nosebleeds and vaginal bleeding. People who have recently coughed up blood or have serious bleeding should not receive Avastin.
According to a statement made by FDA Commissioner Margaret A. Hamburg, M.D.:
“This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use,” Dr. Hamburg said. “After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life.”
Today, however, Avastin is still approved for treatment of certain types of colon, lung, kidney and brain cancer.
The InVite Study
The InVite Study is a collaboration between Genentech and the 23andMe Personal Genome Service to recruit volunteers with breast cancer who have used Avastin in treating their breast cancer before approval of the drug was revoked.
The 23andMe Personal Genome Service is a provider of up-to-date scientific literature as it pertains to an individual’s genomic sequence that may be used toward empowering people with making informed decisions about their genetics and their health. Among the services provided, 23andMe Personal Genome Service provides subscribers with their unique personal genetic profile, including more than 200 health and trait reports and information about their ancestry. Aside from ancestry and genetic health profile analysis, it is also involved in collaborating with research institutions and biotech companies in providing cost-effective online study subject recruitment.
The goal of the InVite Study is to learn more about how genes influence the response to Avastin in the treatment of metastatic breast cancer. In particular, the identification of potential biomarkers that may be used to identify a subset of patients with breast cancer who can tolerate and benefit from Avastin during their breast cancer therapy.
Genentech and 23andMe Personal Genome Services believe that by recruiting study subjects and requesting samples of their DNA that it will:
• Provide a large scale genetic database to correlate with metastatic breast cancer diagnosis and progression, and to better understand why Avastin works well in some patients but causes side effects in others.
• Enable a wider demographic of patients to participate through a web-based, geographically neutral platform.
• Reduce traditional time and cost barriers in cancer research that limit recruitment of an adequately sized study group and control group required for scientific discovery -- the 23andMe research platform has already accelerated the pace of research in Parkinson’s disease and myeloproliferative neoplasms.
• Bring together scientists and actively engaged participants in a collaborative effort to advance understanding of metastatic breast cancer progression and variation in Avastin response.
To become part of the study volunteers need to:
• Send in a saliva sample (collected in a 23andMe DNA kit)
• Take a baseline survey about their breast cancer diagnosis and experience on bevacizumab (also known as Avastin®)
• Answer short follow up questions every three months about any changes in their health or treatment
For their participation in the study, volunteers are provided with a free subscription to some of 23andMe’s genetic services.
InVite Study controversy
However, some health experts are not impressed by the InVite Study and question whether this is a tactic by Genentech to gain re-approval for Avastin for treating breast cancer. According to an article published in the weekend edition of the San Francisco Chronicle, Karuna Jaggar, executive director of Breast Cancer Action in San Francisco, questioned how scientific the results would be.
"This is not a random sample. This is not a representative sample. This is a self-selected group of women who are responding through social media," said Jaggar, whose group supported the FDA's decision. "My question is, who is and who isn't included? Is this a diverse sample?"
Ms. Jaggar’s questions are legitimate and are a reflection of fears that deviating from normal scientific practices in recruiting test subjects for a study by involving a private company in the research could lead to biased results.
However, at this time such fears appear to unwarranted as the study is reportedly designed to perform as an inexpensive way to seek data that could supply leads to future studies that would then be performed under more conventional scientific investigation.
To be fair to Genentech, the researchers are following the advice stated by FDA Commissioner Margaret A. Hamburg, M.D who said that the, “FDA is committed to working with sponsors to bring promising cancer drugs to market as quickly as possible using tools like accelerated approval… I encourage Genentech to consider additional studies to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug.”
Among this select subgroup of women could potentially be those who suffer from Triple Negative Breast Cancer.
Triple Negative Breast Cancer is typically diagnosed based upon the presence, or lack of, three "receptors" known to fuel most breast cancers: estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2). The problem with having this type of breast cancer is that the more successful treatments for breast cancer target these receptors, which women with triple negative breast cancer do not possess and thus the name, "triple negative breast cancer."
With the revoking of approval of Avastin for treating breast cancer, women diagnosed with Triple Negative Breast Cancer lost an important treatment option for their cancer that on an individual basis could result in benefits that outweighed the risks—the same criteria that led to the revoking of approval of Avastin for the general public.
Currently, the InVite Study is seeking to recruit 1,000 patients with metastatic breast cancer who have taken Genentech's Avastin between 2010 and 2011. Follow this link to learn more about how you can participate in the study.
Image Source: Courtesy of Wikipedia