Avodart Increases Prostate Cancer in High Risk Group

[Millard]

http://online.wsj.com/article/BT-CO-20101129-707936.html

The Food and Drug Administration questioned the clinical benefit of using GlaxoSmithKline PLC's (GSK, GSK.LN) Avodart to cut the risk of prostate cancer.

Avodart is currently approved to treat benign prostatic hypertrophy or an enlarged prostate. The company is seeking FDA approval to market the drug to certain men to reduce the risk of prostate cancer. The drug will be reviewed by an FDA advisory panel on Wednesday along with Merck & Co.'s (MRK) Proscar, a drug similar to Avodart.

GlaxoSmithKline conducted a study involving more than 8,000 men considered at high risk of developing prostate cancer. Overall, the study found a 23% reduction in the risk of developing prostate cancer over a four-year period among those treated with Avodart compared to patients receiving a placebo. The company has proposed that men considered at high risk for the development of prostate cancer are those who have had a prior negative biopsy and have an elevated serum prostate-specific antigen, or PSA.

In a document posted to the FDA's website Monday, the agency said the study results involving Avodart "do not appear to confer clinical benefit for the indication under consideration."

The agency said the reduction in prostate cancer risk was driven by prostate cancers considered to be low-risk. There was an increase in prostate cancers considered "high-risk" or those with a so-called Gleason Score of 8 to 10 among patients treated with Avodart compared to those receiving a placebo drug, the FDA said. Higher Gleason Scores indicate more aggressive cancers.

Specifically, 29 high-grade tumors were found among patients being treated with Avodart compared to 19 in the placebo group.

Anne Phillips, a medicines development leader at GlaxoSmithKline, said the company believes Avodart can be safely used to lower the risk of prostate cancer "without interfering with the ability to pick up the high-grade cancer." She noted that men diagnosed with prostate cancer are often treated aggressively even in cases where their tumors are low-grade or low-risk.

Merck is seeking to add the results of a separate clinical study sponsored by the National Cancer Institute that suggested Proscar cut the risk of prostate cancer, although the company isn't seeking FDA approval to market Proscar to reduce the risk of prostate cancer. Proscar is widely available as a generic drug.

The FDA said the proposed label changes "could be interpreted to suggest that Proscar is safe and effective for the prevention of prostate cancer in healthy men."

The agency said there was an increased risk of high-grade cancers among men treated with Proscar and a decreased risk of lower-grade cancers compared to those treated with a placebo over a period of about seven years.


-By Jennifer Corbett Dooren, Dow Jones Newswires


http://online.wsj.com/article/BT-CO-20101129-707936.html

 

[Michael Scally MD]

ODAC meets Wednesday on Proscar/Avodart for prostate-cancer prevention.

FDA briefing doc:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM234934.pdf

MRK (Proscar) briefing doc:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM234935.pdf

GSK (Avodart) briefing doc:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM234936.pdf

 

[Michael Scally MD]

ODAC Rejects Proscar and Avodart for Prostate-Cancer Prevention

[The panel voted 17-0 against Proscar and 14-2 against Avodart due to concern that these drugs might *increase* the risk of the most aggressive form of prostate cancer even while lowering the overall cancer risk. GSK and MRK argue that the drugs do not actually increase the risk of aggressive cancers, but rather increase the *diagnosis* of such cases, an argument that I find plausible.]

http://finance.yahoo.com/news/FDA-panel-rejects-drugs-to-apf-1550784793.html?x=0&sec=topStories&pos=2&asset=&ccode=

By Matthew Perrone
Wednesday December 1, 2010, 6:36 pm EST

WASHINGTON (AP) -- A panel of federal health on Wednesday rejected the use of two drugs from Merck and GlaxoSmithKline to prevent prostate cancer, saying the drugs could actually raise the risk of the most serious types of tumors.

The Food and Drug Administration panel of cancer experts voted 17-0 with one abstention that the risks of Merck's Proscar outweighed its benefits. In a similar vote, the panel voted 14-2 with two abstentions against GlaxoSmithKline PLC's Avodart. Both drugs are already approved to treat enlarged prostate.

"In a setting like this, the onus is on the drug to be completely safe, and to show benefit, and I don't think it reached that level," said panel Chairman Dr. Wyndham Wilson, of the National Cancer Institute.

The FDA is not required to follow the panel's advice, but often does.

Studies by both companies showed their drugs decreased incidence of low-grade prostate tumors by nearly 25 percent.

However, panelists voiced concern that a small number of men taking the drugs actually developed more aggressive tumors, compared with patients taking a dummy pill. Panelists said the risk of increasing deadly tumors outweighed the benefit of reducing tumors that are seldom fatal.

According to figures from the FDA presented Tuesday, for every 60 men treated with Avodart for four years, one serious case of prostate cancer would be prevented. But for every 200 men treated during the same timeframe, one would develop a high-grade tumor.

The head of FDA's cancer drugs division stressed that the drugs must be held to a higher standard than traditional cancer drugs because they would be used in healthy men.

"We're talking about treating potentially hundreds of thousands of people who don't have a disease, as opposed to a small cohort of patients with a disease who need treatment options," said Dr. Richard Pazdur, director of FDA's office of oncology drug products.

Panelists said it was unclear whether the drugs actually cause the higher-grade tumors or simply make them more difficult to detect. Both Avodart and Proscar shrink the size of the prostate and reduce a key protein used to screen for prostate cancer. Additionally, low-grade tumors are often an early warning sign that leads to increased screening of patients, and eventually the detection of more serious tumors.

Currently there are no drugs approved to prevent prostate cancer.

Doctors screen for prostate cancer using physical exams, imaging scans and tests that measure prostate serum levels. Treatment for the disease can include surgery to remove tumors, radiation therapy or chemotherapy.

Glaxo and Merck argued Tuesday that by reducing low-grade tumors their drugs could reduce unnecessary biopsies -- a procedure where a tiny tissue sample is removed and tested for cancer. About 650,000 men had prostate biopsies last year and 70 percent of the tumors sampled were low-grade, according to Glaxo.

But a majority of panelists said reducing biopsies was not good enough.

"I do not see that there was any benefit to this drug in terms of long-term cancer," said Wilson. "The benefit that was put forward was that it reduced the number of patients who might go onto surgery."

Glaxo has asked the FDA for permission to market Avodart as a preventive measure against prostate cancer, while Merck simply wants to add information about reducing prostate cancer to the label of its drug Proscar.