Breast cancer drug Avastin loses FDA support

By Dr. Ananya Mandal, MDNov 21 2011

According to a Food and Drug Administration (FDA) announcement last Friday, 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.

This announcement 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.

However FDA Commissioner Margaret A. Hamburg said the choice was difficult because so many women and their doctors have put their faith in the drug. She said, “I did not come to this decision lightly… Sometimes, despite the hopes of investigators, patients, industry and even the FDA itself, the results of rigorous testing can be disappointing.” Hamburg added that 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. Additionally breast cancer will remain it’s off label use, though insurance companies may not be willing to pay for it.

Avastin 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. It received an accelerated FDA approval 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 paclitaxel experienced six more months of progression-free survival (11.8 months) than patients who took only the chemotherapy drug (5.9 months). 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.

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. This triggered the FDA move to withdraw Avastin's approval for breast cancer patients in December 2010, but the drug's manufacturer, Genentech Inc., challenged the agency.

In February 2011, the UK's National Institute for Health and Clinical Excellence (NICE), the NHS drugs advisory body, said Avastin should not be used to treat secondary breast cancers. NICE, which issues guidance for NHS in England and Wales, said there was insufficient evidence that the drug prolonged life. This guidance followed a recommendation by the European Medicines Agency (EMA) that doctors only prescribe the drug in combination with the taxane drug, paclitaxel.

The drug’s manufacturer, Genentech, which fought long and hard to retain the approval, said it was “disappointed.” The decision could cost Genentech and its Swiss parent company, Roche, up to $1 billion in annual sales. Use of Avastin has already declined to 20 percent, from 60 percent, of American 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. A Genentech spokeswoman said the company would continue to provide some help to breast cancer patients in securing insurance coverage.

“The bottom line is that they are throwing out the baby with the bathwater. There absolutely may be subsets of carefully chosen breast cancer patients who benefit from Avastin,” said Dr Elisa Port, co-director of the Dubin Breast Center of Mount Sinai Hospital in New York. Roche, the Swiss manufacturer of the drug, has said it will undertake further study of the treatment, especially with the chemotherapy drug paclitaxel, to try to identify which patients might be best suited to benefit from use of the drug.