The government delivered a blow to some desperate patients Friday as it ruled the blockbuster drug Avastin should no longer be used to treat advanced breast cancer.

Avastin is hailed for treating colon cancer and certain other malignancies. But the Food and Drug Administration said it appeared to be a false hope for breast cancer: Studies haven’t found that it helps those patients live longer or brings enough other benefit to outweigh its dangerous side effects.

“I did not come to this decision lightly,” said the FDA’s commissioner, Dr. Margaret Hamburg. But she said, “Sometimes despite the hopes of investigators, patients, industry and even the FDA itself, the results of rigorous testing can be disappointing.”

Avastin remains on the market to treat certain colon, lung, kidney and brain cancers. Doctors are free to prescribe any marketed drug as they see fit. So even though the FDA formally revoked Avastin’s approval as a breast cancer treatment, women could still receive it — but their insurers may not pay for it. Some insurers already have quit in anticipation of FDA’s long-expected ruling.

However, “Medicare will continue to cover Avastin,” said Brian Cook, spokesman for the Centers for Medicare & Medicaid Services. The agency “will monitor the issue and evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies.”

Including infusion fees, a year’s treatment with Avastin can reach $100,000.

The ruling disappointed patients who believe Avastin is helping to curb their incurable cancer.

“It’s saved my life,” said a tearful Sue Boyce, 54, of Chicago. She’s taken Avastin in addition to chemotherapy since joining a research study in 2003. Her breast cancer eventually spread to her lungs, liver and brain, but Boyce says she is stable and faring well.

“So I’m hoping the insurance company will grandfather me in to continue taking it,” she said.

The Avastin saga began in 2008, when an initial study suggested the drug could delay tumor growth for a few months in women whose breast cancer had spread to other parts of the body. Over the objection of its own advisers and to the surprise of cancer groups, FDA gave Avastin conditional approval — it could be sold for such women while manufacturer Genentech tried to prove it really worked.

The problem: Ultimately, the tumor effect was even smaller than first thought. Across repeated studies, Avastin patients didn’t live longer or have a higher quality of life. Yet the drug causes some life-threatening risks, including severe high blood pressure, massive bleeding, heart attack or heart failure and tears in the stomach and intestines, the FDA concluded. In two public hearings — one last year and one this summer — FDA advisers urged the agency to revoke that approval.

“The science is clear: Breast cancer patients are more likely to be harmed than helped by Avastin,” said Diana Zuckerman of the National Research Center for Women and Families in Washington.

Genentech had argued the drug should remain available while it conducted more research to see if certain subsets of breast cancer patients might benefit, and some patients and their doctors had argued passionately for the drug.

“There certainly are patients who benefit tremendously,” said Boyce’s oncologist, Dr. Melody Cobleigh of Rush University Medical Center. “We’ll just be battling with the insurance companies.”

“For those not fortunate enough to be on Medicare or an insurance plan that covers it, it’s a death sentence,” Christi Turnage of Madison, Miss., said of the FDA’s decision. Her breast cancer had moved into her lungs before she began Avastin three years ago and the spreading stopped, but Turnage said her insurer is ending coverage and she will seek financial help from Genentech’s access program.

Hamburg said that she considered those arguments but that scientifically there are no clues yet to identify who those rare Avastin responders would be — putting a lot of people at risk in order for a few to get some as-yet-unknowable benefit. She urged Genentech to do that research, saying the FDA “absolutely” would reconsider if the company could find the right evidence.

Genentech, part of Swiss drugmaker Roche Group, pledged to begin that research.

“We are disappointed with the outcome,” said company chief medical officer Dr. Hal Barron. “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 in the United States.”

The breast cancer organization Susan G. Komen for the Cure said that it respected the FDA’s decision and that it was time for researchers to concentrate on finding so-called biomarkers that would tell which drug is right for which patient.

“Each type of cancer is very different from another in important ways, and in the end it’s no surprise that Avastin’s effectiveness may not be equivalent against all types of cancer,” said Dr. Neal Meropol of University Hospitals Case Medical Center in Cleveland, who has long used Avastin for colon cancer.

Associated Press writer Marley Seaman in New York contributed to this report.

Copyright © 2011 The Associated Press. All rights reserved.

Anna Yukhananov, Reuters: August 31, 2011

U.S. health regulators said they would consider setting up a registry that tracks safety problems with breast implants, after too many patients dropped out of company-funded studies.

But the U.S. Food and Drug Administration emphasized on Wednesday that silicone implants were safe and would stay on the market, despite calls for their removal by consumer groups.

Expert advisers who held a two-day meeting to discuss post-approval safety studies for silicone implants urged the FDA to establish a registry.

“We believe it’s a good idea to have a conversation about a breast implant registry. … (But) we believe implants are safe and effective and should remain on the market,” Dr William Maisel, deputy director of the FDA’s devices division, told reporters after the meeting.

In 2006 the FDA approved silicone gel-filled breast implants sold by Allergan and Johnson & Johnson’s Mentor unit on condition both companies follow 40,000 women for 10 years to look at safety issues, as well as extend smaller pre-approval studies.

So far, Allergan has collected preliminary two-year data for 60 percent of participants, while Mentor has collected three-year data for only 21 percent — well below the 65 percent the FDA said would be acceptable.

“It’s very inefficient to enroll 40,000 patients, and only get data on 400 on them (for rare symptoms). So having registries is a much more high-value approach,” said Jason Connor, a biostatistician on the advisory panel.

There were almost 400,000 breast enlargement or reconstruction procedures in the United States in 2010, according to the American Society of Plastic Surgeons. That includes silicone and saline implants.

In June, the FDA said the risks of breast implants are well understood, after looking at the companies’ results as well as reports of negative events and scientific literature. It said women who get silicone implants are likely to need additional surgery within 10 years.

The agency had banned silicone implants for most U.S. women in 1992 after some said the devices leaked and made them chronically ill.

The companies and FDA advisers said patients and their doctors may not have enough incentives to stay in the company-funded studies, especially if they have to fill out a 27-page questionnaire every year, or do expensive medical procedures such as MRIs that test if their implant has ruptured.

A registry, which would track any patient who has had a breast implant, can provide broader data, making it easier to identify any complications, such as rupturing of the device.

Panel members said women should be encouraged to enroll in the registry by linking participation to the warranty on their devices, or to their surgeons’ certification.

Maisel also said it was important to involve different groups, including advocacy groups and physicians, to make sure patients understand the benefits of sharing information about their implants.

“What we’ve heard over the last two days is that it takes a whole community,” Maisel said. “You can have the most well-meaning company, but if the patients don’t want to participate in the study, that’s out of their control.”

However, some groups said the agency was letting manufacturers, especially Mentor, off the hook.

“You can’t ignore the fact that Allergan has three times more patients participating than Mentor. You can’t not hold Mentor responsible for that,” said Diana Zuckerman, president of the National Research Center for Women & Families.

Officials Say They Will Work With Companies to Improve Follow-Up Rates

Gardiner Harris, New York Times: August 31, 2011

WASHINGTON — After two days of discussion and testimony about silicone breast implants, a top government health official said he had heard nothing to shake his faith in the safety of the widely used implants.

The official, Dr. William Maisel, chief scientist for the Food and Drug Administration’s Center for Devices, said silicone breast implants were safe.

“We felt that way before the meeting, and we continue to feel that way after the presentations and discussions over the past two days,” Dr. Maisel said.

There are risks to the implants, however, Dr. Maisel said, including ruptures, a hardening of the area around the implants, the need to remove the implants, scarring, pain, infection and asymmetry. “Women should feel assured that the F.D.A. continues to believe that currently marketed silicone breast implants are safe,” he said.

Some patients and women’s groups who testified at the meeting disagreed.

Diana Zuckerman, president of the National Research Center for Women and Families, a research and education group, told an expert panel that the two companies that manufacture silicone breast implants — Johnson & Johnson and Allergan — had done a poor job of studying patients who got the implants, as the F.D.A. required them to do.

“And without proper data, we still don’t know how safe or effective they are and whether there are certain patients at risk for extremely negative outcomes,” Ms. Zuckerman said.

Dr. Maisel agreed that the studies conducted by the two companies had failed to follow as many patients as the agency had hoped.

One purpose of this week’s meeting was to ask the expert panel what the agency and the two companies should do about that poor follow-up. Some suggested that patients should be paid for participating; others mentioned that doctors should get some money, too.

There was some criticism of the 27-page research form that patients who participate in the study are required to complete and whether it could be shortened. Nearly all expressed hope that a registry could be created that would follow all breast implant patients, but such registries are expensive to maintain and complicated to create.

The committee also agreed that patients should no longer be told that they should get a magnetic resonance imaging test three years after getting implants and every two years following.

The reason for telling patients to get M.R.I.’s is that silicone breast implants sometimes rupture without women being aware, and an M.R.I. can reveal this unseen problem.

But many patients ignore the requirements because M.R.I.’s are expensive and it is not clear what they should do when an unseen rupture is discovered; the risks associated with ruptured implants may not be greater than the risks of the operation needed to take them out.

“F.D.A. continues to believe, as does the panel, that M.R.I. is the gold standard for evaluating breast implants for silent rupture,” Dr. Maisel said. “But there was consensus among the panel that the requirements for ongoing M.R.I.’s should be removed.”

Dr. Maisel promised that the F.D.A. would study whether to follow this advice.

Rita Rubin, MSNBC: June 22, 2011

More than one in five women who had silicone breast implants for cosmetic purposes and half of those who got the implants after a mastectomy needed surgery to remove the implants within a decade, according to a Food and Drug Administration report out Wednesday.

“Recognize that breast implants are not lifetime devices,” says the FDA report on the longest studies on the implant to date. “The longer you have your implants, the more likely it will be for you to have them removed.”

In 2010, U.S. surgeons performed nearly 400,000 breast implant procedures. About three-quarters were for breast augmentation, while the rest were for breast reconstruction. About half the surgeries used silicone gel implants; the other half used implants filled with saline.

Silicone implants were pulled off the market in 1992, after concerns were raised about lack of safety data and worries that leaking silicone was linked to immune-system disease.

But the FDA returned the implants to the market in November 2006 after clinical trials didn’t find a link to feared diseases. Plastic surgeons and some women were clamoring for the return of the silicone versions because they say they look and feel more real than saline, which can ripple because it’s essentially a sack of salt water.

The approval required implant makers Allergan and Mentor to conduct large 10-year studies following up on patient experiences, and Wednesday’s report is the first glimpse at how the breast implants held up.

The FDA says 20 to 40 percent of patients who get silicone implants for cosmetic reasons will need another operation to modify or remove them within 10 years. For women with implants for breast reconstruction, the number is even higher, at 40 to 70 percent. The biggest issue was scar tissue hardening around the implant.

Other complications include implant rupture, wrinkling, asymmetry, pain and infection, the report said. Women with breast implants are also slightly more likely to be diagnosed with anaplastic large cell lymphoma, a rare form of cancer.

Despite the risk of complications, the FDA believes that silicone implants are reasonably safe, the report said.

But women in the studies had a high dropout rate and so other complications or long-term safety issues might be missed, the agency’s report says.

Mentor has three-year data for only one out of every five women in its study, while Allergan has two-year data for three out of every five, according to the FDA’s safety update.

“Low follow-up rates and other study limitations may limit interpretation of the data and preclude the detection of very rare complications,” the agency concluded.

Without knowing why patients have dropped out of the studies, it’s impossible to reach any conclusions about implant safety, says Diana Zuckerman, president of the nonprofit National Research Center for Women & Families in Washington, D.C.

“Did they stop going to the doctor because their implants were removed?” Zuckerman says. “Did they stop going because they died or got very sick? Or are they so happy with their implants that they skipped follow-up visits?”

The FDA has been working with the companies to improve patients’ participation in the studies and will convene a meeting of outside experts to discuss the issue later this summer, says William Maisel, deputy director for science and chief scientist at the agency’s Center for Devices and Radiological Health.

Most women who get breast implants are in their 20s and 30s, and may mistakenly consider breast implants a one-time investment.

“They need to understand they’re going to need many removals and replacements for the rest of their lives,” Zuckerman says.

Alicia Mundy and Jon Kamp, Wall Street Journal: February 15, 2011

Most of the medical devices recalled in recent years because of serious or life-threatening hazards were initially cleared for market through an abbreviated approval system that doesn’t require testing on patients, according to a study in the Archives of Internal Medicine.

The study by a Washington health-research group and the Cleveland Clinic’s Steven Nissen comes after the Food and Drug Administration proposed changes to tighten the faster approval system, known as 510(k), but put off some of its toughest proposals for further study under pressure from device makers.

Of 113 medical devices that were subject to recalls between 2005 and 2009, 80 were allowed on the market through the 510(k) program, the study found. About a third of the recalled devices were cardiovascular products, including several brands of external defibrillators.

“These findings suggest that reform of the regulatory process is needed to ensure the safety of medical devices,” said the authors. The lead author, Diana Zuckerman, heads the National Research Center for Women & Families, a group that has advocated stiffer approval standards for medical devices.

The 510(k) process is popular with the industry because it can save time and money in regulatory reviews, and industry lobbyists have been campaigning on Capitol Hill against radical revisions to the program.

The process requires that the proposed device be similar to a product already marketed, and is intended for low and moderate-risk devices.

The industry’s lobbying group, the Advanced Medical Technology Association, or AdvaMed, said the study is flawed because it looks at the number of recalls without comparing that to the number of devices that didn’t have problems. AdvaMed-supported studies say that more than 99% of the devices cleared through 510(k) don’t face recalls.

Overall, the 510(k) program has a “remarkable safety record with extremely low recall rates,” AdvaMed said. […]

A 510(k) costs the FDA an average of about $20,000 per application compared to more than $800,000 for a full device review by the agency, according to the report. A full review includes evaluation of safety-and-efficacy clinical trials. […]

Read the original article here.