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 fueled doubts about its value for treating breast cancer for years.
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.
"Sometimes, despite the hopes of investigators, patients, industry and even the FDA itself, the results of rigorous testing can be disappointing," she said.
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's available, doctors will have the flexibility to prescribe it for breast cancer patients as an off-label use, though insurance companies may not be willing to pay for it.
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 $50,000 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 only took the chemo drug. It was the first medicine to be okayed 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, since 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. The FDA moved to withdraw Avastin's approval for breast cancer patients in December 2010, but the drug's manufacturer, Genentech Inc., challenged the agency.
Medications that are fast-tracked 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.
Hopes that Avastin could prolong life for patients with advanced breast cancer rested on a 2007 study in the New England Journal of Medicine.
Researchers found that patients who took the drug in combination with the chemotherapy agent paclitaxel experienced an 11.8-month window, on average, during which their cancer was not growing. That compared with an average of 5.9 months of progression-free survival among patients who received standard chemotherapy alone.
But even in that study, patients on Avastin did not live longer, said Dr. Kerin Adelson, a medical oncologist at Mount Sinai School of Medicine in New York.
A later study confirmed the lack of survival benefit from Avastin while bringing the drug's risks into better focus, Adelson said.
"Many drugs will improve the amount of time it takes for a cancer to grow but don't improve the amount of time a patient lives," she said. "For Avastin, that was the situation."
The drug generated about $3.5 billion in sales in the United States in 2010. But sales have fallen this year since the FDA advisory committee recommended that approval for breast cancer patients be withdrawn.