FDA committee votes down 5-ARIs for prostate cancer risk reduction

December 16, 2010

An FDA Oncologic Drugs Advisory Committee has voted against the use of two 5-alpha-reductase inhibitors for reducing the risk of prostate cancer in men at risk for the disease.

An FDA Oncologic Drugs Advisory Committee has voted against the use of two 5-alpha-reductase inhibitors for reducing the risk of prostate cancer in men at risk for the disease.

Regarding the supplemental new drug application for dutasteride (Avodart), the committee voted 14-0, with two abstentions, that the risks of the drug for this indication outweigh the benefits, according to the Associated Press. For finasteride (Proscar), the committee voted 17-0, with one member abstaining.

Dutasteride manufacturer GlaxoSmithKline was seeking permission to add prostate cancer risk reduction to its drug’s label. Finasteride manufacturer Merck was not seeking a cancer risk reduction indication but attended the meeting at the request of the FDA. Both drugs are FDA-approved for the treatment of BPH.

The data reviewed by the committee included results from two large-scale studies of the drugs: the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. Both found that the drugs reduced overall prostate cancer risk by 23% to 25%. However, the studies also found small increases in the incidence of higher-grade cancers in those taking the drugs compared with those taking placebos.

"The FDA advisory committee decision is very disappointing," Leonard G. Gomella, MD, professor and chairman of urology at Thomas Jefferson University’s Kimmel Cancer Center, Philadelphia, told Urology Times. "We have a significant burden of over-diagnosis and over-treatment of prostate cancer, and this class of drugs appeared to offer a solution.

"Although the REDUCE trial demonstrated a risk reduction in a large number of men, the committee chose to focus on a small number of high-grade cancers and determined that this class of drugs is inappropriate for prostate cancer risk reduction, even in the population of men with elevated PSA and previous negative biopsy," added Dr. Gomella, a co-investigator of the REDUCE trial. "This decision will certainly reduce the enthusiasm for further large-scale, long-term studies of any prostate cancer chemoprevention or risk-reduction strategy."

Editor’s note: News of the committee’s decision was published after Urology Times went to press with an article in which Dr. Gomella discusses the drugs’ use in reducing prostate cancer risk (“Data analysis will help clarify role of PCa prevention,” December 2010, page 1).