The FDA ( Food and Drug Administration ) has announced that the Agency is recommending removing the breast cancer indication from the label for Avastin ( Bevacizumab ) because the drug has not been shown to be safe and effective for that use.
The Agency is making this recommendation after reviewing the results of four clinical studies of Avastin in women with breast cancer and determining that the data indicate that the drug does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. These risks include severe high blood pressure; bleeding and hemorrhage; the development of perforations in the body, including in the nose, stomach, and intestines; and heart attack or heart failure.
In July 2010, after reviewing all available data an independent Advisory Committee, composed primarily of oncologists, voted 12-1 to remove the breast cancer indication from Avastins label.
Subsequent studies failed to confirm the benefit observed in the original trial. None of the studies demonstrated that patients receiving Avastin lived longer and patients receiving Avastin experienced a significant increase in serious side effects. The limited effects of Avastin combined with the significant risks led FDA to this decision. The results of these studies are disappointing.
Removing the breast cancer indication from the Avastin label will be a process. This is the first step. The drug itself is not being removed from the market and this action will not have any immediate impact on its use in treating breast cancer. The action will not affect the approvals for colon, kidney, brain, and lung cancers.
Oncologists currently treating patients with Avastin for metastatic breast cancer should use their medical judgment when deciding whether a patient should continue treatment with the drug or consider other therapeutic options.
The Agency has informed Genentech, Avastins manufacturer, of its proposal to withdraw marketing approval of the drug for breast cancer. Genentech has not agreed to remove the breast cancer indication voluntarily, so the agency has issued a Notice of Opportunity for a Hearing, which permits Genentech to request a public hearing if it wishes to contest the agencys determination. The company has 15 days to request a hearing; if it does not do so, the hearing will be waived, and FDA will begin proceedings to remove the breast cancer indication.
Avastin, in combination with chemotherapy ( Paclitaxel ), was approved in february 2008 under the FDAs accelerated approval program, based on the results of a clinical trial known as E2100, which evaluated the drug in patients who had not received chemotherapy for their metastatic HER2-negative breast cancer. Under the accelerated approval program, a drug may be approved based on clinical data that suggest the drug has a meaningful clinical benefit, with more information being needed to confirm this. The program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted.
After the accelerated approval of Avastin for breast cancer, Genentech completed additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on progression-free survival without evidence of an improvement in overall survival or a clinical benefit to patients sufficient to outweigh the risks. The small increase in progression-free survival reflects a small, temporary effect in slowing tumor growth.
Avastin has also been associated with several other serious and potentially life-threatening side effects including the risk of stroke, wound healing complications, organ damage or failure; and the development of a neurological condition called reversible posterior leukoencephalopathy syndrome, characterized by high blood pressure, headaches, confusion, seizures, and vision loss from swelling of the brain.
On the basis of all available data relating to the use of Avastin to treat metastatic breast cancer, the agency has determined that the risks of the drug outweigh the benefits for this use.
Source: FDA, 2010