The Food and Drug Administration on Dec. 16 recommended removing bevacizumab’s indication as a breast cancer therapy.

The actual removal of the indication—if it ultimately happens—could take months, as the manufacturer of bevacizumab (Avastin), is being given the opportunity to appeal the decision.

The FDA’s action does not impact bevacizumab’s other approvals. And, while the appeals process continues, bevacizumab will remained approved for breast cancer, agency officials said.

Oncologists who want to continue treating breast cancer patients with bevacizumab “should use their medical judgment,” Dr. Richard Pazdur, director of the FDA’s Office of Oncology Drug Products, said in a briefing announcing the agency’s decision.

The decision has been awaited by oncologists and the breast cancer community since at least mid-July, when in a near-unanimous vote, the FDA’s Oncologic Drugs Advisory Committee recommended that the approval of bevacizumab as a first-line treatment for patients with metastatic breast cancer be withdrawn. That recommendation was based on results of follow-up studies that failed to confirm progression-free survival benefits in this population.

“I understand that today’s recommendation is disappointing for patients with breast cancer,” Dr. Pazdur said. “Please note these results are also disappointing for the FDA as well,” he said, adding that he had been hopeful that survival improvements seen in the E2100 study that supported the drug’s accelerated approval in 2008 would bear out in later studies.

But because bevacizumab entered the U.S. market through the accelerated approval process, the agency has the power to remove the drug if subsequent trials do not bear out initial results.

Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, agreed with Dr. Pazdur that agency officials did not take the withdrawal lightly. She said that FDA staff who reviewed the bevacizumab data “have close, personal experience with this disease” and that they were oncologists “who have treated patients with cancer and have been personally touched by this disease.”

The FDA is hopeful that bevacizumab still has promise, said Dr. Woodcock. “We don’t doubt based on the data that this is an active drug,” she said, but added that despite a tumor response, there had been no survival benefit demonstrated.

In the briefing, agency officials painstakingly laid out how the FDA came to its decision. The agency took into account the E2100 study, which evaluated bevacizumab use in patients who had not previously received chemotherapy for their metastatic HER2-negative breast cancer; these patients showed a five-month improvement in survival. They also evaluated three more studies that FDA reviewers said did not replicate that benefit: AVADO, RIBBON1, and AVF2119g.

In addition, patients taking bevacizumab had a higher risk of serious side effects, including stroke, wound healing complications, organ damage or failure, and the development of a neurological condition called reversible posterior leukoencephalopathy syndrome (RPLS). Given these side effects, the risk of using bevacizumab outweighed its benefits, officials said.

Genentech was given 15 days to appeal the agency’s decision, which the company said it would do, even as the briefing was being conducted.

The company now has 30 days to submit a package to the agency with data and evidence that “there are material facts in dispute” to be granted the hearing, Denise Esposito, deputy director of the FDA’s Office of Regulatory Policy, said in the briefing.

If the agency grants a hearing, it will be announced in the Federal Register. It would be a public hearing, with outside experts invited to participate but not vote, said Ms. Esposito. It’s possible those experts could be some or all members of the advisory committee that previously voted on bevacizumab. Genentech also would be allowed to make its case.

The agency would then take time to make a decision, said Ms. Esposito. She said the whole process could take at least several months.

The FDA’s decision follows the recommendation made earlier in December by the National Institute for Health and Clinical Excellence. That body, the clinical effectiveness agency for England and Wales, recommended against use of bevacizumab in combination with taxane chemotherapy for metastatic breast cancer, citing high costs and an unclear survival benefit.

The European Medicines Agency ruled on Dec. 16, however, that the benefits of bevacizumab in combination with paclitaxel outweigh its risks and said, “This combination remains a valuable treatment option for patients suffering from metastatic breast cancer.” The agency added that bevacizumab should not be used in combination with docetaxel for breast cancer.

Dr. Pazdur said he could not speculate why the EMA had reached a slightly different conclusion on the same data reviewed by the FDA. But, he said, the FDA was acting within the rules laid out by the accelerated approval process, whereas the EMA had fully approved bevacizumab based on the E2100 trial results.

The drug also recently failed to improve pathological complete response in a large, European trial among women with primary HER2-negative breast cancer who were given a neoadjuvant regimen that combined bevacizumab with epirubicin, cyclophosphamide, and docetaxel. The results were reported at the San Antonio Breast Cancer Symposium.

FDA: Bevacizumab Should No Longer Be Indicated for Breast Cancer