The rare decision by the Food and Drug Administration is supported by many cancer experts but drew fierce opposition from cancer patients and some doctors who defend the drug and say it should remain available.
The ruling is a significant setback for the world's best-selling cancer drug and will likely cost Swiss drugmaker Roche hundreds of millions of dollars in lost revenue. Avastin is also approved for various types of colon, lung, kidney and brain cancer.
FDA officials stressed that the recommendation is only a preliminary step toward revoking the drug's approval for breast cancer. Roche has refused to voluntarily withdraw the indication, and the company said in a statement it would request a public meeting on the issue.
Drug companies almost always follow FDA requests, and agency officials said a meeting over the fate of Avastin would be the first of its kind. The agency said it will consider whether to hold the meeting in the coming months.
"Today's decision was a difficult one for the agency but certainly not unique," said Dr. Janet Woodcock, director of FDA's drug center. "The FDA is responsible for assuring that the products we approve for patients are both effective and safe."
The FDA approved Avastin for breast cancer in 2008 based on one study suggesting it halted the spread of breast cancer for more than five months when combined with chemotherapy. But follow-up studies showed that the delay lasted no more than three months, and patients suffered dangerous side effects.
"Given the number of serious and life-threatening side effects, the FDA does not believe there is a favorable risk-to-benefit ratio," said Dr. Richard Pazdur, FDA's chief of cancer drug review.
In a separate announcement Thursday, the European Medicines Agency said it would keep the drug available as a combination treatment with the chemotherapy drug paclitaxel - the same use rejected by the FDA.
FDA officials said the split opinion was due to differences in how Avastin was approved in the U.S. versus Europe. The FDA cleared the drug under its accelerated approval program, giving the agency the option to rescind approval if follow-up studies didn't confirm initial results. European regulators granted the drug full approval based on the same results, making it more difficult to reverse course when faced with weaker follow-up results.
If the FDA ultimately removes Avastin's breast cancer indication, doctors will still have the option to prescribe the drug "off-label," or without a federal approval, but many insurers do not reimburse drugs for such uses. Without insurance coverage, Avastin's enormous cost would put it out of reach for most patients. Roche sells the drug at a wholesale price of $7,700 a month. When infusion charges are included, a year's treatment with Avastin can run more than $100,000, though Roche caps spending at $57,000 per year for patients who meet certain financial criteria.
For the time being, the FDA said the drug will remain available and patient care will not be affected.
While vigorously opposed by thousands of cancer patients, the FDA's ruling is in line with the guidance of its outside panel of cancer experts, who voted 12-1 in July to rescind the drug's approval for breast cancer.
Cancer specialists said Avastin never lived up to its initial promise.
"The bottom line is that it doesn't work very well," said Dr. Albert Braverman, chief of oncology at State University of New York Downstate Medical Center. "I've seen the occasional patient have a brief remission, which is nice, but it's certainly not doing anything important. It's not saving anyone's life."
But some patients credit their survival to Avastin and say the FDA's decision could amount to a death sentence.
Christi Turnage of Madison, Miss., said her cancer has been undetectable for more than two years since starting therapy with Avastin. She was diagnosed with breast cancer in June 2006 and began taking the drug in 2008 after the tumors spread, or metastized, to her lungs. Breast cancer that spreads to other parts of the body is generally considered incurable.
"It's a miracle drug for me and for several of my friends, and to deny it to women being diagnosed with metastatic disease is wrong," Turnage said.
More than 9,500 cancer patients and friends and family signed a petition by Turnage urging the FDA to keep Avastin approved.
Dr. Julie Gralow of the Seattle Cancer Care Alliance said the drug appears to work in some subsets of patients and should remain available.
"It is clear that some breast cancer patients derive substantial benefit from Avastin. We don't know how to select those tumors or patients yet," said Gralow, who helped conduct the initial study of Avastin in breast cancer.
Barbara Brenner, director of Breast Cancer Action, a San Francisco-based advocacy group, said the group agrees with FDA's decision.
"It's never been shown to improve survival or quality of life. We know that people will be disappointed, but science has to dictate where we go with drug approval," Brenner said.
She added that women already receiving the drug should be allowed to keep getting it.
Roche reported Avastin sales of nearly $6 billion in 2009.
FDA rules bar the agency from considering cost when making drug approval decisions. But earlier this month the U.K.'s public health service rejected the drug for breast cancer, citing its high cost and limited benefit.
U.S. sales of Avastin for breast cancer generate an estimated $600 million annually, according to analyst David Kaegi of Switzerland's Bank Sarasin. When combined with lost revenue from the U.K., Kaegi estimated Roche's Avastin sales could fall by $1 billion.
The FDA granted Avastin accelerated approval for breast cancer in 2008 based on a study suggesting it delayed the spread of breast cancer for more than five months when combined with a popular chemotherapy drug. However, patients taking the drug did not actually live longer than those taking chemotherapy alone. And FDA officials reiterated Thursday that all four studies of Avastin conducted by Roche failed to show increased survival.
Avastin, which is grown from hamster ovary cells, was the first drug approved to fight cancer by stopping nutrients from reaching tumors. Such "targeted therapies" were thought to hold promise for eliminating chemotherapy, but that promise has gone unmet. Today drugs like Avastin are generally used as a second-line treatment after chemotherapy.
"I think a few years down the line it was becoming increasingly clear, at least to me, that this wasn't a particularly active drug, despite the initial presentation," said Dr. Braverman, referring to Avastin for breast cancer. "But people are sort of on a roll and it takes a while for things to die down."
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AP Medical Writer Marilynn Marchione contributed to this report from Milwaukee.
