The Food and Drug Administration (FDA) is recommending removal of 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 recommendation follows a review of the results of four
clinical studies of Avastin in women with breast cancer and a determination
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.
Risks to users
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.
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 Avastin's label.
"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."
Woodcock said the limited effects of Avastin combined with
the significant risks is responsible for the decision. "The results of these
studies are disappointing," she added. "We encourage the company to conduct
additional research to identify if there may be select groups of patients who
might benefit from this drug."
Other applications
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, nor will it 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.
Genentech notified
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.
Accelerated approval
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, FDA determined.
The small increase in "progression-free survival" reflects a small, temporary
effect in slowing tumor growth.
'Life-threatening' side effects
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 says it is willing to work 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.
