FDA withdraws approval of Avastin to treat breast cancer

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 for years about its value for treating breast cancer.

Still, FDA Commissioner Margaret A. 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 for which its 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 upwards 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 more months of progression-free survival than patients who took only the chemo drug. It was the first medicine to be OKd 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 rigorous continued review, and “withdrawal is an essential component of the accelerated approval program,” Hamburg 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’s action.


“It does not improve survival,” said Dr. Joanne Mortimer, director of the Women’s Cancers Program at City of Hope in Duarte, 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 death from stroke or heart attack, 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 than it was for 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 in patients receiving 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 Avastin’s failure to extend survival, and brought the drug’s risks into better focus, Adelson said. (One of her own breast cancer patients who took Avastin had a massive stroke, she 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. It’s not known how many U.S. patients with breast cancer took the drug, but doctors said it was commonly prescribed in cases of metastatic disease.

Officials with Genentech Inc., the South San Francisco company that makes Avastin, expressed disappointment with the FDA’s action but said a new Phase 3 clinical trial would begin soon to further evaluate how the medication works with paclitaxel. In addition, research will proceed on the search for biomarkers that may indicate whether a particular woman is likely to benefit from the drug.


Some researchers said they still believed it may help certain subgroups of women with breast cancer, such as people with so-called triple-negative disease, which is a particularly aggressive form.

“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.”

But Meropol said that he agreed with the FDA’s decision and applauded the time and diligence the agency gave in weighing the matter.

“I think the FDA made a very reasoned decision based on the scientific data as well as input from experts, patients and the people who make Avastin,” he said.


Patient groups were divided on the decision, largely because of how insurers will deal with the issue.

Leaders of the Ovarian Cancer National Alliance, based in Washington, worried that the removal of Avastin’s indication for breast cancer might harm women with ovarian cancer who receive the medication off-label.

Some breast cancer patient advocates have harbored doubts about Avastin in spite of its popularity.

“Our position from the very beginning is that they should not have given this particular drug approval for breast cancer,” said Fran Visco, president of the National Breast Cancer Coalition in Washington, who applauded the decision.


The loss of Avastin in the breast cancer treatment arsenal should not concern patients, since they can still receive chemotherapy, Mortimer said. “There are so many new drugs coming out for treatment of breast cancer.”

Alexa Vaughn in the Washington bureau contributed to this report.