Avastin Loses Approval From F.D.A. to Treat Breast Cancer
Published: November 18, 2011 - New York Times
The commissioner of the Food
and Drug Administration on Friday revoked the approval of the drug Avastin
as a treatment for breast
cancer, ruling on an emotional issue that pitted the hopes of some desperate
patients against the statistics of clinical trials.
The commissioner, Dr. Margaret
A. Hamburg, said that clinical trials had shown that the drug was not
helping breast cancer patients to live longer or to meaningfully control their
tumors,
but did expose them to potentially serious side effects like severe high
blood pressure and hemorrhaging.
gSometimes, despite the hopes of investigators, patients, industry and even
the F.D.A. itself, the results of rigorous testing can be disappointing,h Dr.
Hamburg told reporters Friday. gThis is the case with Avastin when used for the
treatment of metastatic breast cancer.h
Avastin will remain on the market as a treatment for other types of cancers,
so doctors can use it off-label for breast cancer. But insurers might no longer
pay for the drug, which would put it out of reach of many women because it costs
about $88,000 a year.
Federal officials said on Friday that Medicare
would still provide coverage for the drugfs use in breast cancer, though the
government plans to gmonitor the issue and evaluate coverage options.h
The drugfs manufacturer, Genentech,
which fought long and hard to retain the approval, said it was gdisappointed.h
The decision could cost Genentech and its Swiss parent company, Roche, up to $1
billion in annual sales. Use of Avastin has already declined to 20 percent of
American patients with newly diagnosed metastatic breast cancer, from 60
percent, according to Genentech.
A Genentech spokeswoman said the company would continue to provide some help
to breast cancer patients in securing insurance coverage. But it will no longer
provide co-payment assistance and will no longer cap combined expenses for many
patients and their insurers at $58,000 a year.
Dr. Hamburgfs decision, outlined
in a 69-page memorandum, agrees with the unanimous recommendation made by an
F.D.A. advisory committee in June, at the end of a two-day hearing at which some
women taking the drug pleaded for its continued approval.
gIfm disappointed the commissioner has chosen to take the hardest line
possible,h Terrence D. Kalley of Troy, Mich., whose wife, Arlene, has been
taking Avastin, said Friday. Mr. Kalley, who organized a protest outside the
F.D.A. hearing in June, said that for some women, Fridayfs decision was gnothing
short of a death sentence.h
The decision could also be grist for opponents of health
care reform. Senator David Vitter, Republican of Louisiana, accused the
F.D.A. on Friday of grationing accessh to treatment. The F.D.A. has insisted
that cost issues were not considered. Yet some advocacy groups praised the
decision. gIt is the right decision for women and for science,h Frances M.
Visco, president of the National
Breast Cancer Coalition, said in an e-mail. gWe all wished the drug worked.
It does not.h
The administration has pledged to make decisions on the basis of science.
That made it difficult for Dr. Hamburg to go against the conclusions of the
F.D.A.fs own staff and the outside experts on its advisory committee.
There was also pressure to uphold the integrity of the accelerated program
that was used to approve Avastin for breast cancer in 2008. That program allows
the F.D.A. to provisionally approve drugs with less than the usual evidence of
effectiveness, subject to further confirmation.
The agency has been criticized for failing to make sure the follow-up studies
are done, or to remove approvals if those studies did not confirm the expected
benefit. The case of Avastin, in which subsequent studies did not show the same
level of effect as the initial study, is one of only a few in which an approval
has been revoked and the first one in which the manufacturer had requested a
hearing to appeal the proposed revocation.
Daniel Carpenter, a professor of government at Harvard and author of the book
gReputation and Power: Organizational Image and Pharmaceutical Regulation at the
F.D.A.,h said in an e-mail that the decision would make it easier for the agency
to take more risks in granting accelerated approval because gwith Avastin, the
agency has sent a message that accelerated approval is neither absolute nor
irreversible.h Even before the decision Friday, a handful of insurers had
stopped paying for Avastin as a treatment for advanced breast cancer. Most
insurers had said they would wait for the commissionerfs decision before
evaluating their policies.
Medicare is obligated to pay for off-label use of cancer
drugs that are listed in certain references, like the one published by the National
Comprehensive Cancer Network, an organization of major cancer hospitals. In
July a committee of breast cancer specialists from those centers reaffirmed that
Avastin should remain listed as gan appropriate therapeutic option for
metastatic breast cancer.h A third of the committee members had financial ties
to Genentech, according to Dr. Hamburgfs memorandum.
It appears Avastin has lost its perch as the worldfs best-selling cancer drug
to Rochefs own Rituxan, a lymphoma medicine. Global sales of Avastin in the
first nine months of 2011 declined 8 percent, to 3.94 billion Swiss francs, or
about $4.3 billion, Roche reported. In the United States alone, sales fell more
sharply, down 15 percent to 1.77 billion Swiss francs, or $1.93 billion.
An initial clinical trial that was the basis for the provisional approval
showed that Avastin, when combined with the drug paclitaxel, which is also known
by the brand name Taxol, delayed the progression of disease by about five and a
half months, compared to use of paclitaxel alone.
But in subsequent studies, in which Avastin was combined with different chemotherapy
drugs, tumor
growth was delayed by only one to three months. And Avastin did not prolong
lives at all, nor did it improve quality of life.
Many breast cancer specialists say that Avastin does appear to work very well
for some patients, and some advocates have said the drug should be left on the
market for the sake of those patients. But Dr. Hamburg said there was no way to
determine in advance who those patients were, so many women would use the drug.
gThe evidence does not justify broad exposure to the risks of this drug,h she
wrote.