June 28, 2011 -- An unusual and closely watched hearing on the fate of Avastin as a treatment for advanced breast cancer got off to an emotional start on Tuesday, with federal advisors listening to testimony from patients, doctors, and advocacy groups.
Many urged the FDA to reconsider its decision to withdraw approval for Avastin as a treatment for advanced breast cancer.
"I owe my life to Avastin," said Patricia Howard, age 66, of New York, who has been treated for breast cancer since 2005. "I'm not just a piece of anecdotal evidence. I'm a wife, mother, sister, aunt, friend, and grammy."
But others applauded the agency's decision.
Christine Brunswick, vice president of the National Breast Cancer Coalition, said she has also been diagnosed with metastatic breast cancer. "I can personally attest to how devastating this disease is."
She said scientific studies have not proven that the drug is safe or effective as a breast cancer treatment.
"We must accept and act on evidence or we will never make the needed progress we so desperately want," she says. "We now know that women died because of this drug."
Controversy Over Avastin
Avastin is a drug that shrinks tumors by choking off their blood supply.
It was first approved in 2004 to treat metastatic colorectal cancer. Since then, it has also been approved to treat advanced non-small-cell lung cancer, metastatic renal cell carcinoma, and glioblastoma brain tumors.
In 2008, against the recommendation of its advisors, the FDA approved Avastin for breast cancer through an accelerated approval process that allows a therapy to be marketed to the public based on preliminary clinical findings, pending further studies to confirm its safety and effectiveness.
That approval was based on the results of a single clinical trial which found that Avastin prevented breast cancer from progressing for an average of 5.5 months longer in women who took Avastin combined with the chemotherapy drug paclitaxel, compared to women taking paclitaxel and a placebo.
No other studies have been able to repeat that result, however.
Four subsequent studies considered by the FDA have found that Avastin improves progression-free survival by about two months compared to standard chemotherapy, but it doesn't improve overall survival. In some tests of the drug, more women taking Avastin died compared to those on standard chemotherapy.
This slight difference in progression-free survival "comes at a toxicity cost," says Lee H. Pai-Sherf, MD, a medical officer in the FDA's Division of Biologic Oncology Products.
Those studies have also shown that breast cancer patients taking Avastin have higher rates of adverse events compared to standard chemotherapy drugs. One study found that half of women taking Avastin experienced episodes of bleeding, a rate that was twice as high as women on a standard chemotherapy drug.
Other serious side effects experienced by women on the drug include high blood pressure, heart attacks, heart failure, protein in the urine (a sign of kidney damage), and gastrointestinal perforations -- holes in the lining of the stomach or intestines.
Accelerated Approval Program
Genentech, the company that makes Avastin, is appealing that decision and has taken the rare step of requesting a public hearing. The company will present its case tomorrow.
Today, regulators took pains to lay out the evidence they used to conclude that Avastin should no longer be prescribed for breast cancer.
"The totality of the data show that the Avastin has only a modest effect on PFS [progression-free survival], and this small effect, in the absence of an effect on overall survival or patient quality of life, does not outweigh its substantial and life-threatening risks," says John K. Jenkins, MD, director of the office of new drugs at the FDA's center for drug evaluation and research.
Jenkins called withdrawal "the right public health decision."
If the FDA sticks by its withdrawal of Avastin's approval for breast cancer, the drug, which can cost as much as $100,000 a year, will remain on the market, but insurance companies are less likely to cover it for that use.
Breast cancer patients would also lose access to the drug through the company's patient assistance program, which caps the drug's annual cost at about $58,000.
Since 1995, Jenkins says, the FDA has granted 49 indications for cancer drugs through its "accelerated approval" process.
At least three of those drugs failed to show clinical benefit and later had their approvals revoked.
The FDA reported in a study published in March in the Journal of the National Cancer Institute that 14 other drugs have failed to complete the required confirmatory trials.
Some of those drugs have been allowed to remain on the market for more than 10 years without any additional evidence to back up their safety and efficacy, a fact the FDA says undermines the integrity of the accelerated approval program.
Genentech has asked the FDA to keep Avastin available for breast cancer while it conducts another study.
In response, Jenkins says the agency can't allow "protracted marketing of drugs that have not been shown to be safe and effective while sponsors take numerous bites at the apple in an effort to confirm clinical benefit."