With obvious reluctance, Food and Drug Administration officials are recommending that the cancer drug Avastin no longer be approved to treat breast cancer.
The move was directed at Roche's Genentech unit, maker of Avastin, and reflects the FDA's hope the company would voluntarily withdraw the drug as a treatment for certain kinds of breast cancer because data from four studies show the benefits don't outweigh the risks.
But Genentech isn't going along with the FDA's plan. The company wants to keep marketing Avastin for breast cancer and is seeking a hearing with FDA to make the case.
Genetech's response sets up an unprecedented conflict. An FDA lawyer says it will be the first time a manufacturer hasn't heeded the agency's request to voluntarily withdraw a drug for a use that was approved quickly but with some strings attached.
It's up to FDA Commissioner Margaret Hamburg to decide whether to grant Genentech the hearing.
While this process unfolds, women with advanced breast cancer can continue to take Avastin. And the FDA says the Centers for Medicare and Medicaid Services will continue to pay for the $88,000-a-year drug. Presumably private insurers will too.
But clearly, women who are convinced that Avastin is helping them will be on tenterhooks in the meantime.
In a media teleconference to announce the decision, FDA officials alluded to the lobbying that breast cancer patients and their advocates have done to keep Avastin available. Dr. Janet Woodcock, head of the FDA's Center for Drug Evaluation and Research, put it this way:
I'd like to thank the dozens of patients and their family members and friends who have personally reached out to me and other colleagues at FDA to share their personal experiences with the disease and with their treatment with Avastin and breast cancer. We do not want to discount those experiences and we wish those patients continue success.
But after reviewing the results of three studies, FDA officials decided there was no evidence Avastin prolonged the life of women with advanced breast cancer more than the use of older chemotherapy drugs alone. These are women whose cancer has recurred at the initial site or has metastasized outside the breast.
Back in February 2008, the FDA relied on a single study that hinted Avastin combined with chemotherapy prolonged what's called progression-free survival from breast cancer by about five months, compared to chemotherapy alone.
That means the tumor didn't grow as determined by X-ray or CT studies. But the FDA, in granting fast-track conditional approval to Avastin, said it wanted other studies that confirmed this benefit or better still indicated that patients actually lived longer on Avastin. Three additional studies, it says, failed to show that benefit.
But Avastin has caused serious and even life-threatening side effects, such as perforation of the stomach or intestines, problems with surgical wound-healing, hemorrhage, and an unusual neurologic condition involving headaches, confusion, seizure and vision loss associated with brain swelling.
FDA officials acknowledge there may be some breast cancer patients for whom Avastin works. But studies to date don't point to any such subgroup, and it will take years before further studies can answer that question.
Whatever happens with the FDA's proposal to withdraw approval for breast cancer will not affect Avastin's use for cancer of the colon, kidney, brain and lung. The drug's presumed advantage in those cancers is that it retards the development of blood vessels that tumors need to grow.