The Burrill Report


The U.S. Food and Drug Administration has revoked its approval for the use of Genentech’s Avastin in breast cancer saying the drug has not been shown to be safe or effective for that use.

“After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks,” says FDA Commissioner Margaret Hamburg. “Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life.”

The decision, outlined in a 69-page opinion from Hamburg, involves Avastin used in combination with the cancer drug paclitaxel for patients who have not been treated with chemotherapy for a form of metastatic breast cancer known as HER2 negative. The decision does not affect Avastin’s approved use as a treatment for certain types of colon, lung, kidney, and brain cancer.

The controversy surrounding the use of Avastin in breast cancer has been at times heated, emotional, and politically charged. Oncologists and the breast cancer community are divided over its use. The expense of the drug—$88,000 a year for a breast cancer treatment—has led some to suggest the FDA was taking the steps for financial rather than health reasons and pointed to it as a form of rationing that would become more common under healthcare reform efforts. The FDA, though, has insisted its decision has been driven by science.

For Roche, which acquired Genentech in 2009, the stakes are high. Analysts have previously estimated the company stands to lose $1 billion a year in sales were Avastin to lose the indication of breast cancer. Already, the controversy has curtailed its use. Avastin sales have fallen and some insurers have already said they would not pay for use of the drug in breast cancer patients.

Hal Barron, chief medical officer and head of global product development for Genentech, expressed disappointment in the FDA’s decision, but said the company will move forward with studies to see if it can identify possible subpopulations of breast cancer patients that will benefit from Avastin. “Despite today's action, we will start a new phase 3 study of Avastin in combination with paclitaxel in previously untreated metastatic breast cancer and will evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin.”

Avastin was approved for metastatic breast cancer in February 2008 under the FDA’s accelerated approval program, which allows a drug to be approved based on data that are not sufficiently complete to permit full approval. The accelerated approval 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 two additional clinical trials and submitted the data from those studies to the FDA. Those studies were required to justify continued approval of Avastin in the indication. But the data showed only a small effect on tumor growth without finding evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone–not enough to outweigh the risk of taking the drug, the FDA said.

Avastin’s risks include severe high blood pressure; bleeding and hemorrhaging; heart attack or heart failure; and the development of perforations in different parts of the body such as the nose, stomach, and intestines.

Genentech fought efforts by the agency to revoke the approval. In a two-day hearing in June over the matter, the FDA’s Oncologic Drugs Advisory Committee voted 6-0 in favor of withdrawing approval of Avastin in the breast cancer indication. That followed an earlier 12-1 vote by the committee to withdraw approval for Avastin in breast cancer.

Because Avastin will remain on the market, doctors will still be able to prescribe it for breast cancer patients on an off-label basis. The question, though, is whether patients under their coverage will be able to pay for it. The FDA’s decision will provide insurers who were waiting for the ruling before reevaluating their policy, justification to stop paying for the drug.


November 18, 2011
http://www.burrillreport.com/article-fda_revokes_avastin_approval_in_breast_cancer.html