FDA revokes Avastin approval for breast cancer. Decision leaves some devastated. Drug will remain available to treat other cancers.

Washington Post|November 19, 2011

By Rob Stein

The Obama administration revoked approval on Friday of the top-selling cancer drug Avastin for treating advanced breast cancer, despite appeals from distraught women, some patient advocates and the company that makes the drug.

Food and Drug Administration Commissioner Margaret A. Hamburg issued a 69-page decision that said a review had clearly shown the drug was harming women more than it was helping them. Studies have found that Avastin can increase the risk of dangerous bleeding, heart attacks and other problems.

“Sometimes, despite the hopes of investigators, patients, industry and even the FDA itself, the results of rigorous testing can be disappointing,” Hamburg said. “This is the case with Avastin when used for the treatment of metastatic breast cancer.”

While medical advances have reduced the death toll from breast cancer, the malignancy remains the most common cancer among women, and the decision leaves few last-ditch options for many of those fighting the most advanced form of the disease. As a result, the fate of the drug had sparked one of the more emotional and acrimonious debates in years over a medical treatment among patients, oncologists, women’s health advocates, health-care policymakers, politicians and the pharmaceutical industry.

Some patients likened the FDA decision to a death sentence. Advocates of quicker access to new treatments and critics fearing health-care rationing called it a prime example of government overstepping. But many leading researchers, public health analysts and even prominent breast cancer doctors and advocates praised the decision. They saw it as a crucial demonstration that careful examination of the scientific evidence trumped emotion and intense public pressure.

Despite the revocation, Avastin will remain available to treat other cancers, enabling doctors to prescribe it “off-label” for breast cancer patients. But several insurance companies have already stopped paying for the drug for breast cancer, and the decision will probably prompt more to follow. Avastin costs about $99,000 a year per patient. Breast cancer patients also will lose eligibility for a program sponsored by drugmaker Genentech that caps the annual cost at about $58,000 for women making less than $100,000 a year and helps cover insurance co-payments.

Medicare, however, will continue to pay for Avastin, at least for now, officials said. Genentech’s foundation also will help women who do not have insurance or whose insurance refuses to pay for it, and will refer women to other charitable groups that could help them, said company spokeswoman Charlotte Arnold.

“We are disappointed with this outcome. We remain committed to the many women with this incurable disease and will continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment,” she said.

The decision was condemned by some patient advocacy groups.

“By not recognizing the fact that a subgroup of women with metastatic breast cancer respond well to Avastin, we have yet another tragic mistake by the FDA,” said Frank Burroughs, founder of the Abigail Alliance, which advocates for greater access to new treatments. “Because of FDA drug rejections like Avastin for breast cancer, the terribly slow FDA approval of lifesaving therapies and the FDA’s blocking of compassionate access, we are losing thousands of lives of cancer patients and others with serious life-threatening illnesses each year.”

‘I am stunned’

Individual patients also expressed outrage and despair.

“I am devastated,” said Patricia Howard, 66, of Summerfield, Fla., who pleaded with the FDA’s advisory committee to retain the approval. “I am stunned by the lack of compassion of the FDA for those of us who are successful on this drug. . . . Every time I sit in the infusion chair I worry if this will be my last infusion.”

In a statement, J. Leonard Lichtenfeld, deputy chief medical officer of the American Cancer Society, said he hoped that, at the very least, insurance companies would continue to pay for the drug for women “with metastatic breast cancer who are currently on the drug and who are showing a benefit from its use.”

Several major insurance companies contacted Friday said they were reviewing their positions on Avastin in light of the FDA’s revocation.

The decision was praised by many others, including several leading breast cancer advocacy groups and experts who said it was important for the agency to base its decisions on the results of careful clinical studies, not emotional appeals, especially when lives are at stake and controlling health-care costs is so crucial to the nation’s economy.

“We should be using our time and resources to find drugs that work. It is unfortunate that Avastin does not,” said Fran Visco, president of the National Breast Cancer Coalition, a patient advocacy group. “Marketing campaigns and appeals by the public devastated by breast cancer cannot change that. These women deserve drugs that well-designed research tells us will prolong their lives. Let’s focus our attention on making that happen.”

Among the costliest

The FDA is not supposed to acknowledge cost in drug approvals, and officials have stressed that the price was irrelevant. But coming amid a continuing national debate over President Obama’s health-care overhaul, the fight about Avastin has become entangled in the politically sensitive struggle over medical spending and effectiveness.

“The fact remains that thousands of women today depend on Avastin as a vital tool in their fight against breast cancer, and the FDA should not have taken that option off the table by rationing access,” said Sen. David Vitter (R-La.)

Avastin is among the costliest of a new generation of anti-cancer medications that appear to offer some patients perhaps a few extra months of life. It was the first drug designed to fight cancer using a new strategy – inhibiting blood flow to tumors – and was approved for treating several malignancies. Evidence is much clearer that the approach is effective for colon, lung, kidney and brain cancer.

Avastin for breast cancer has been controversial since its approval in 2008. Only one study found that the drug appeared to slow the growth of an advanced breast tumor, delaying progression by about 51 / 2 months. It remained unclear whether patients lived longer or enjoyed a better quality of life. So the FDA authorized Avastin under a special program designed to make advances in treatment available to patients quickly. The deal was that Genentech must validate the risk-benefit ratio with additional studies.

The agency moved in December to revoke the approval based on a July 2010 advisory committee conclusion that the new studies had not shown that the drug extends life and had indicated that it slowed tumor growth for far less time – perhaps as little as a month.

At the same time, the drug increased the risk for life-threatening bleeding and hemorrhaging, heart attacks, heart failure, severe high blood pressure and perforations in different parts of the body, including the nose, stomach and intestines.

Genentech immediately challenged that decision. That led the agency to convene a two-day meeting in June, which was marked by unusually tense exchanges between representatives of Genentech and agency officials. In the end, the six-member committee concluded that the drug was doing more harm than help.

New research vowed

On Friday, the company vowed to start a new study of Avastin in combination with another drug in metastatic breast cancer patients to “evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin,” Arnold said.

Before the FDA announced initial plans to revoke Avastin’s approval for breast cancer, the drug was being prescribed annually to about 60 percent of the 29,000 U.S. women with breast cancer who were eligible. Globally, Avastin had annual sales of about $5.5 billion in 2010, making it the world’s best-selling cancer drug and one of the top-selling products for Genentech and Roche, its Swiss owner.

Genentech has waged an unprecedented campaign to keep U.S. approval of the drug for breast cancer. But as questions have been raised about its safety and effectiveness, sales and use of the drug have dropped significantly for breast cancer in the United States, falling to about 20 percent of eligible women, according to Genentech.

“The science is clear: Breast cancer patients are more likely to be harmed than helped by Avastin,” said Diana Zuckerman, president of the National Research Center for Women & Families. “The risks of the drug are very substantial and can be fatal, killing patients long before they would otherwise die from the disease. FDA made a scientific decision, and it was absolutely the right decision.”

Staff writer N.C. Aizenman contributed to this report.