Avastin Decision Not Based On Cost: FDA Official
6 CommentsBy Ed Silverman // January 7th, 2011 // 9:37 am
The debate over the breast cancer indication for Avastin was one of the more highly charged issues last year. After clinical studies revealed the Roche med did not prolong overall survival and caused serious side effects, an FDA panel recommended withdrawing approval. To the applause of some consumer advocates (see here), the agency last month took that step, even though many breast cancer patients urged the FDA to preserve an option they say worked for some people (look at this).
After deciding to unravel the indication, however, the FDA was criticized by Republicans for using cost as a reason - the treatment carries a price tag of about $80,000 a year - amid growing concern that healthcare rationing is becoming an issue for regulators. Now, however, Richard Pazdur, who heads the FDA’s Office of Oncologic Drugs, denies that cost was a factor and tells The Wall Street Journal that Roche’s Genentech unit was repeatedly warned some key data were inadequate.
“We made the decision because the drug has a marginal effect on tumor growth in breast cancer and in light of Avastin’s severe side effects, the risks outweigh the limited benefit,” he tells the paper, noting that docs can continue to prescribe the med, which is approved to treat bowel, lung, brain and kidney cancers. Insurers, however, are unlikely to cover the cost of breast cancer treatment.
In pointing to data, Pazdur cites a study called E2100 that Genentech argued showed Avastin can delay tumor growth in patients with advanced breast cancer for five months. “There were always issues with this trial (and) problems,” he tells the paper, adding the FDA told Genentech years ago that the trial lacked needed standards to demonstrate efficacy in breast cancer.
The trial, which began in 2001, “wasn’t originally proposed as a drug approval study” for breast cancer, Pazdur notes, something that Genentech confirmed. Why does this matter? If E2100 had originally been designed for that purpose, tighter controls would have been needed to ensure standard data collection and objective readings of scans assessing tumor growth, the paper writes.
FDA records and reports from public meetings in 2007 and 2010 say E2100 is missing about 10 percent of the X-ray follow-up scans, according to the Journal. An independent review of patient-scan data came to different conclusions from study investigators numerous times, Pazdur says, calling it a “serious discordance” that cast doubt on the trial results.
Although Pazdur described patient anecdotes as moving, he argues those do not qualify as scientific evidence. “People need to understand that breast cancer patients have only been taking Avastin in combination with Taxol,” says. There may be a subset of women with breast cancer who could be helped by Avastin, but Genentech needs to figure out who they are, he adds.
One insurer hailed the FDA decision. Allan Korn, chief medical officer of the national Blue Cross and Blue Shield Association, tells the paper that “The FDA made a difficult but correct choice in withdrawing approval for Avastin in breast cancer. We owe patients evidence-based treatments that improve survival and quality of life. Otherwise, we offer only false hope.”
But Joseph Sparano, a cancer doctor at Montefiore-Einstein Center for Cancer Care in New York, whose group has done Avastin research for Genentech, criticized the agency. When taken with Taxol, he says Avastin has helped delay tumors spreading to other organs in some of his patients. “Those patients desperately need as many options as possible,” he tells the paper.
For its part, Genentech is appealing the FDA decision and asked for a formal hearing.
Greg Pawelski
For decades, X-rays have been the principal means for researchers to judge whether a cancer drug works. The FDA released a report some years back that lists more than 12 research areas that need to be addressed to try to improve clinical trials. Among the efforts is a search for new ways to measure cancer progression. There is growing evidence that X-rays, long the standard, may not accurately assess a patient’s disease.
Katherine Panageas, Dr.P.H., of Memorial Sloan-Kettering Cancer Center in New York, and colleagues examined the use of progression-free survival (PFS) as an endpoint measurement in clinical trials. They felt that measurement of progression-free survival has methodological flaws that can lead to biased estimates.
PFS is measured as the time from start of treatment to the first measurement of cancer growth. Disease progression is typically measured by radiologic tests, such as x-rays, at scheduled intervals. Most often, researchers do not know when progression actually occurs, so they can only estimate that it happened sometime between the test that showed progression and the previous one.
Methodological problems can arise when researchers define the date of progression as the date on which it was first detected, even though progression most likely occurred prior to that day. The researchers compared a variety of surveillance intervals using a simulated population to demonstrate how the evaluation schedule can affect the estimation of PFS.
The researchers found that the outcome of the trial can be heavily influenced by the surveillance interval and that comparing the PFS times of two studies with different evaluation schedules can lead to erroneous conclusions.
“The decision to use PFS as a primary endpoint should be considered carefully in the design phase of the trial. It is our intention to make researchers aware that estimates of PFS are highly dependent on when they look for progression. The clinical research community can address this concern by adopting consistent strategies for interval evaluations in the design phase.”
sven
This is a lame WSJ piece that adds nothing new to what everyone already knows. Everything Pazdur said is spelled out in the FDA’s decision memo on Avastin. Politicians and their young staff know so little about FDA… Show us any evidence that FDA has ever used a cost basis in its approval/rejection decisions. PLEASE.
Searching2000
Greg:
You put a lot of effort into your comment - or you ‘re-purposed’ an existing piece. Either way, you certainly have the right to comment.
My question is - what is the linkage to this current post … unless you are working off the text below?
“FDA records and reports from public meetings in 2007 and 2010 say E2100 is missing about 10 percent of the X-ray follow-up scans, according to the Journal. An independent review of patient-scan data came to different conclusions from study investigators numerous times, Pazdur says, calling it a “serious discordance” that cast doubt on the trial results.”
Greg Pawelski
Searching
It was from a Panageas, et al study published in the March 2007 issue of the Journal of the National Cancer Institute.
Searching2000
Greg:
Then if it was a direct quote, the reference was in order, I think. I believe that Katherine S. Panageas, DrPH would appreciate the acknowledgment. Although the link could be a search, I grant you, here’s the best I could do ‘in 40 seconds’:
http://jnci.oxfordjournals.org/content/99/6/428.abstract?ijkey=9a235b89a8797680e3531759ad21ddb76369cc3a&keytype2=tf_ipsecsha
Still unanswered, however, is the linkage between the quote and Ed’s post - was it the item I suggested? Or did you have a different point to make?
Greg Pawelski
Search
Thanks for the link to update my queue, which suffered a crash this past year. I acknowledged Panageas in my initial comment. The point I was making had to do with X-ray follow-up scans which have been the principal means for researchers to judge whether a cancer drug works (progression-free survival). These tests are performed for the benefit of drug companies seeking new drug approval. However, there should be better ways to measure success of drugs against cancer (i.e. meaningful endpoints), and X-rays may not accurately assess a patient’s disease.