LOS ANGELES — The cancer drug Avastin should not be used to treat breast cancer that has spread to other organs because it doesn’t help patients enough to justify its risky side effects, the Food and Drug Administration ruled Friday.
The decision comes five months after an FDA advisory committee recommended that the federal agency withdraw its approval of Avastin for breast cancer patients. Clinical trial results have for years fueled doubts about its value for treating breast cancer.
Still, FDA Commissioner Margaret Hamburg said the choice was difficult because so many women and their doctors have put their faith in the drug and lobbied hard on its behalf.
“I did not come to this decision lightly,” she said. “Sometimes, despite the hopes of investigators, patients, industry and even the FDA itself, the results of rigorous testing can be disappointing.”
Avastin will remain on the market for treating other types of cancer where the benefits clearly outweigh the risks, such as lung, kidney and colon cancer, Hamburg said. As long as it is available, doctors will have the flexibility to prescribe it for breast cancer patients as an off-label use, although insurance companies might not be willing to pay for it.
Medicare, however, will continue to pay for Avastin, at least for now, officials said.
Harsh side effects
The drug, among the top-selling cancer therapies, is a biological antibody designed to interfere with the blood supply that feeds a tumor and helps it grow and spread. But it can cause harsh side effects, including heart attacks and strokes. It’s also among the most expensive cancer therapies, costing upward of $88,000 a year.
The FDA approved Avastin for metastatic breast cancer in 2008 after a study in the New England Journal of Medicine showed that patients who took it in conjunction with a chemotherapy drug experienced six additional months of progression-free survival compared with patients who took only the chemo drug.
It was the first medicine to be OK’d under an accelerated approval program that allowed it to be used while researchers gathered additional data to clarify its safety and efficacy.
The approval was controversial at the time because an FDA advisory panel had voted against the drug in a 5-4 decision just a few months earlier.
Two subsequent studies showed that Avastin seemed to slow tumor growth significantly in breast cancer patients but did not extend survival.
That soured experts charged with monitoring new data on the drug’s pros and cons.
Maker challenges FDA
The FDA in December moved to withdraw Avastin’s approval for breast cancer patients, but the drug’s manufacturer, Genentech Inc., challenged the agency.
Fast-tracked medications require a rigorous continued review, Hamburg said.
“We do believe withdrawal is an essential component of the accelerated approval program,” she said.
Avastin’s ability to help patients with advanced breast cancer live longer has always been in doubt, and few experts expressed surprise at the FDA action.
“It does not improve survival,” said Dr. Joanne Mortimer, director of the Women’s Cancers Program at City of Hope in Duarte, Calif., who served on two of the three FDA advisory panels that debated Avastin’s use for breast cancer. “Yes, it keeps your cancer under control longer. But . . . the risks are pretty huge.”
Studies showed that women with advanced breast cancer taking Avastin had a higher risk of deaths from strokes and heart attacks and that the medication raised blood pressure and increased the risk of congestive heart failure. The risk of serious bleeding was five times higher among users of Avastin compared with those on chemotherapy only.
Sales have fallen
The drug generated about $3.5 billion in sales in the United States in 2010. Sales have fallen this year since the FDA advisory committee recommended that approval for breast cancer patients be withdrawn.
Use of Avastin has declined to 20 percent, from 60 percent, of U.S. patients with newly diagnosed metastatic breast cancer, the condition for which the drug was approved, according to Genentech. About 29,000 women each year are found to have metastatic breast cancer.
Officials with Genentech expressed disappointment with the FDA’s action but said a new Phase 3 clinical trial will begin soon to further evaluate how the medication acts with the chemotherapy agent paclitaxel. In addition, research will proceed on the search for bio markers that might indicate whether a particular woman is likely to benefit from the drug.
Some researchers said they still think it might help certain subgroups of women with breast cancer.
“This is definitely not the end of the story for Avastin and breast cancer,” said Dr. Neal Meropol, chairman of the American Society of Clinical Oncology’s comparative effectiveness research task force and an oncologist at University Hospitals Case Medical Center in Cleveland. “It’s quite likely there is a subset of patients who benefit from Avastin to a major degree. The challenge for us is to identify which patients with breast cancer will benefit.”
The New York Times contributed to this report.
Facts and figures
29,000 Number of U.S. women each year who are found to have metastatic breast cancer
20 percent Portion of U.S. women with newly diagnosed metastatic breast cancer who take Avastin, down from 60 percent before the FDA announced initial plans to revoke approval
$88,000 High-end cost of a year’s worth of Avastin
$6.8 billion Annual global sales for Avastin in 2010, making it the world’s best-selling cancer drug
