By Rob Stein
Washington Post Staff Writer
Monday, August 16, 2010; A01 - Washington Post

Federal regulators are considering taking the highly unusual step of rescinding approval of a drug that patients with advanced breast cancer turn to as a last-ditch hope.

The debate over Avastin, prescribed to about 17,500 women with breast cancer a year, has become entangled in the politically explosive struggle over medical spending and effectiveness that flared during the battle over health-care reform: How should the government balance protecting patients and controlling costs without restricting access to cutting-edge, and often costly, treatments?

The Food and Drug Administration is reviewing the recommendation of influential scientific advisers to revoke authorization of the drug to treat metastatic breast cancer. Contrary to initial research, new studies indicate that the benefits of the expensive drug, which costs $8,000 a month, do not outweigh its risks, the advisory panel concluded.

Citing a dearth of evidence of the drug's effectiveness, its potential toxic side effects, and its high cost, many cancer experts, patient advocates and others are welcoming the prospect that Avastin's authorization for breast cancer might be repealed. But the possibility is alarming other cancer specialists, women taking the drug, some members of Congress and advocates for giving patients as much access to as many treatments as possible.

The FDA is not supposed to consider costs in its decisions, but if the agency rescinds approval, insurers are likely to stop paying for treatment.

"It's hard to talk about Avastin without talking about costs," said Eric P. Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston. "For better or worse, Avastin has become in many ways the poster child of high-priced anti-cancer drugs."

Avastin is the world's best-selling cancer drug, with global sales of $5.8 billion, and it is the top-selling product for Roche, whose Genentech unit makes it. Its use to treat breast cancer brings in about $855 million in annual revenue in the United States.

Avastin is approved for use in treating several cancers, including those of the colon, lung, kidney and brain. So doctors could continue to write prescriptions for it for breast cancer, as an "off-label" use. But in addition to prompting insurers including Medicare to stop paying for Avastin, an FDA revocation of approval for its use in breast cancer treatment might mean that breast cancer patients would lose eligibility for a program in which Genentech caps the annual cost of the drug at $57,000 for women with annual incomes of less than $100,000.

Avastin was the first drug designed to fight cancer by blocking blood flow to tumors, which has been hailed as one of the first significant innovations in decades in the war on cancer. But Avastin is also one of the most expensive of a new generation of anti-cancer medications that only eke out a few extra months of life.

The FDA endorsed Avastin for advanced breast cancer in 2008 despite divided opinion about its usefulness for that purpose. Only one study had found that the drug appeared to delay an advanced breast tumor from growing by about five months. It remained unclear whether patients actually lived longer or experienced an improved quality of life.

But the FDA approved Avastin under a special program designed to make new treatments available as quickly as possible, with the caveat that pharmaceutical companies conduct follow-up studies validating their drug's effectiveness. The agency has been criticized for failing to adequately review such approvals. Only one of at least 90 drugs that have received accelerated approval has been pulled.

An FDA advisory committee voted 12 to 1 on July 20 to withdraw Avastin's authorization for advanced breast cancer based on two new studies that the advisers concluded had failed to show that the drug actually extends life. Not only that, the committee concluded that the studies indicated the drug slowed tumor growth for even less time -- perhaps as little as about a month. "The vast majority opinion of the committee was that the drug was not doing very much, and what it was doing was more than offset by the negative," said Wyndham Wilson of the National Cancer Institute, who chaired the committee. Avastin can cause a variety of potentially serious side effects, including blood clots, bleeding and heart failure. "In our best judgment, we did not feel this drug was safe to give relative to its benefits," Wilson said.

The recommendation has been praised by many cancer experts and by advocates for breast cancer patients.

"The FDA should never have approved Avastin for breast cancer to begin with," said Fran Visco of the National Breast Cancer Coalition. "We don't see evidence of benefit, but we do see evidence of harm."

But the company disputes the committee's interpretation of the studies, saying they demonstrated that the drug reduced the risk of a woman's cancer progressing or her risk of death from the cancer by 31 to 52 percent.

"It's our opinion that when we look at the data, they are clinically meaningful," said Sandra Horning, who heads cancer research for San-Francisco-based Genentech. "Avastin should continue to be an option for women."

The FDA is not required to follow the advisory committee's recommendation, but it usually does. A decision is expected by Sept. 17. The prospect of Avastin losing authorization for breast cancer has prompted despair among women taking the drug, and some have started petition drives to persuade the FDA to ignore the panel's recommendation.

"I'm very upset," said Leslie Twohig, 48, of Lothian, Md., who has been taking Avastin for eight months and credits the drug with helping her survive. "How long will I be able to stay on Avastin? Are they going to take it away? I know it's working for me. Right now I am able to enjoy my life. Every morning I wake up and wonder how long it's going to go on."

"I am very concerned about people who are receiving the drug and may feel threatened that they may not be able to receive it," said the Dana-Farber Cancer Institute's Winer, who is also chief scientific officer for Susan G. Komen for the Cure, a breast cancer patient advocacy group. "This is not a worthless drug by any means. There is almost certainly a group of women who get a big benefit. "

Several members of Congress have sent protest letters to the FDA and the Department of Health and Human Services.

"I fear this is beginning of a slippery slope leading to more and more rationing under the government takeover of health care that is being forced on the American people," said Sen. David Vitter (R-La.).

But others said that the weight of the evidence was clearly against Avastin and that cost must not be ignored.

"Patients with late-stage cancer are often desperate for help and grasp at straws," said Richard A. Deyo of the Oregon Health and Science University. "Without this regulatory move, the drug would continue to be used and would presumably not benefit anyone and add a lot of treatment costs."