Avastin not safe to treat breast cancer says FDA

by Aimee Keenan-Greene

The U.S. Food and Drug Administration now says Avastin (bevacizumab) can not be used to treat breast cancer because the drug has not been shown to be safe and the risks outweigh the benefits.

The move comes after the FDA reviewed the results of four clinical studies involving breast cancer and Avastin last July. They determined the drug does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression. 

Risks from taking Avastin 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.  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.

Avastin itself is not being removed from the market and this FDA decision will not affect its approval for treating colon, kidney, brain, and lung cancers.

“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.”, Woodcock added.

Breast cancer forms in tissues of the breast, usually the ducts- the tubes that carry milk to the nipple,  and lobules - the glands that make milk. 

The National Cancer Insititute estimates there will be more than 207, 000 new cases of breast cancer diagnosed in the US this year. Almost 40,000 women will die from the disease.

Removing the breast cancer indication from the Avastin label will be a process, until then, 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.

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 patient access to promising new drugs to treat serious or life-threatening conditions sooner, 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.

The FDA informed Avastin’s manufacturer, Genentech, of its proposal to withdraw marketing approval of the drug for breast cancer. Genentech did not agree to remove the breast cancer indication voluntarily. A Notice of Opportunity for a Hearing, which permits Genentech to request a public hearing if it wishes to contest the agency’s determination, has been issued.  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.

The FDA says they are willing 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.