The Burrill Report


The U.S. Food and Drug Administration says it is recommending removing breast cancer as an indication for the use of Genentech’s Avastin from the drug’s label because data have failed to demonstrate it is safe and effective for that purpose.

The decision comes after the agency reviewed the results of four clinical studies of Avastin in women with breast cancer and determined 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. In July 2010, an independent advisory committee composed primarily of oncologists, voted 12-1 to remove the breast cancer indication from Avastin's label after reviewing available data.

“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,” says Janet Woodcock, 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 FDA was careful to note that Avastin is not being removed from the market and its action will not have any immediate impact on its use in treating breast cancer. The action will also not affect the approvals for Avastin’s use in colon, kidney, brain, and lung cancers.

Separately, the European Medicines Agency said that it concluded that Avastin in combination with docetaxel should no longer be used in the treatment of breast cancer because of an imbalance between benefits and risks. However, it said it confirmed that the combination of Avastin with paclitaxel is a valuable treatment option for patients with metastatic breast cancer.

“We are pleased that the EMA has confirmed the benefits of Avastin with paclitaxel and that Avastin will continue to be available for women with metastatic breast cancer living within the European Union,” says Hal Barron, chief medical officer and head, Global Product Development for Genentech. “We believe women living in the United States with metastatic HER2-negative breast cancer should also have Avastin as a treatment option, and, therefore, we will request a hearing with the FDA.”

Op-Ed pieces in anticipation of the FDA action have suggested that the FDA would take the action to restrict Avastin’s use as part of efforts by the Obama Administration to reign in healthcare spending. Avastin can cost up to $90,000 a year. A piece in the Washington Times carried the headline “Will the FDA let women die?
'Access denied' isn't the message Obama should deliver.”

But the FDA in a Q&A posted on its website stated that cost was not a factor in the decision and said it 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.

Avastin, in combination with chemotherapy (paclitaxel), was approved in February 2008 under the FDA's accelerated approval program. 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 for confirmation. 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 been associated with several serious and potentially life-threatening side effects including 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.

While some patients have decried the FDA’s decision, some patient advocates have commended the agency saying the trials showed the drug did not extend life for patients with metastatic breast cancer.

On the Breast Cancer Action website, a statement from the organization’s program manager says, “We must give patients meaningful new options in treatment, and not false promises.”


December 17, 2010
http://www.burrillreport.com/article-fda_to_revoke_avastin%e2%80%99s_approval_as_breast_cancer_treatment.html