Posted: Dec 16, 2010 9:57 PM
Avastin maker Genentech (owned by Roche) will ask the FDA to reconsider at a formal public hearing. Until then -- or until FDA rejects the hearing request -- Avastin will continue to be FDA approved for breast cancer.
Today's action does not affect Avastin's approval for treatment of advanced colon, lung, kidney, and brain cancers.
"I understand the FDA decision is disappointing for patients with breast cancer. It is disappointing for the FDA as well," Richard Pazdur, MD, director of the FDA's oncology drug office, said at a news teleconference.
"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," Hal Barron, MD, chief medical officer and head of global product development for Genentech, said in a news release.
In a 12-1 vote last July, an expert advisory panel urged the FDA to withdraw Avastin's approval for breast cancer. The panel found that the drug's risks outweigh any benefit it might have for breast cancer patients.
The FDA's earlier approval was based on a clinical trial in which Avastin in combination with a common form of chemotherapy (paclitaxel) delayed the growth of metastatic breast cancer by 5.5 months. However, the trial was stopped early and no significant effect on overall survival was seen.
That was enough for the European Medicines Agency, the European Union's version of the FDA. The EMA granted full approval to Avastin for breast cancer treatment in combination with paclitaxel.
The FDA took a different approach. In 2008 -- against the advice of an earlier expert panel -- it granted only a conditional, expedited form of approval for Avastin's use in breast cancer. To get full FDA approval, Genentech was required to submit additional clinical trial data showing that the drug could extend overall survival. The typical patient with metastatic breast cancer survives 18 to 24 months after diagnosis.
Three new studies submitted to the FDA by Genentech not only failed to show an improvement of overall survival, but also failed to show that Avastin could delay tumor progression was well as it had in the first trial.
The three new trials used different chemotherapies than the first trial. Because of this, the European drug agency yesterday reaffirmed its approval of Avastin plus paclitaxel, but not for other chemotherapy combinations. The FDA feels differently, said Janet Woodcock, MD, director of the FDA's center for drug evaluation and research.
"The EMA accepts the magnitude of [delayed tumor progression seen in the first study] as a clinical benefit," Woodcock said at the news conference. "Now we have other trials with a much smaller increase in [delayed tumor progression], no additional benefit, increased side effects, and no increase in survival. So these subsequent trials did not show a clinical benefit."
The studies did show that Avastin carries a number of risks. In addition to the common side effects of nosebleed and high blood pressure, serious side effects include massive bleeding; perforation of the nose, stomach, and intestines; severe high blood pressure; blood clots, heart attack; kidney damage, wounds that do not heal; and a condition called RPLS characterized by headache, confusion, seizures, and vision loss.
Despite these risks, many women facing metastatic breast cancer have petitioned the FDA to retain their access to Avastin. Without FDA approval, Avastin might not be reimbursed by insurance companies -- or by Medicare/Medicaid, which had postponed its decision on whether to cover this use of the drug pending the FDA action. The wholesale price of Avastin is $7,500 a month, which does not include infusion costs.
The FDA is not allowed to consider cost in its approval decisions.
The FDA says it will work with Genentech to design clinical trials to explore whether there is a subset of women with metastatic breast cancer who benefit from Avastin. But Patricia Keegan, MD, director of the FDA's division of biologic oncology products, said at the news conference that the four clinical trials submitted to the FDA offer no hint about which women might benefit.