FDA Takes Action to
Stop Use of Avastin for Breast Cancer: Not Proven Safe, Effective
No studies showed
patients receiving Avastin lived longer, but some did experience a
significant increase in serious side effects
Dec. 16, 2010 -
The Food and Drug Administration announced today 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. In July, after reviewing all available data an
independent advisory committee, composed primarily of oncologists, voted
12-1 to remove the breast cancer indication from Avastin’s label.
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 (or “holes”) in the body, including in the
nose, stomach, and intestines; and heart attack or heart failure.
“After careful
review of the clinical data, we are recommending that the breast cancer
indication for Avastin be removed based on evidence from four
independent studies,” Janet Woodcock, M.D., director of the FDA’s Center
for Drug Evaluation and Research.
“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 us to this difficult decision. The results of
these studies are disappointing. We encourage the company to conduct
additional research to identify if there may be select groups of
patients who might benefit from this drug.”
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 today’s action will not have any immediate impact on its use in
treating breast cancer. Today’s 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, Avastin’s 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
agency’s 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 FDA’s 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 (RPLS), 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.
FDA is open to
working with Genentech on any proposals to conduct additional studies of
Avastin in patients with metastatic breast cancer designed to identify a
population of patients in which the drug’s benefits exceed the risks.
Dec. 16, 2010 -
The Food and Drug Administration announced today 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. In July, after reviewing all available data an
independent advisory committee, composed primarily of oncologists, voted
12-1 to remove the breast cancer indication from Avastin’s label.