Neither dutasteride (Avodart; Glaxo SmithKline) nor finasteride (Proscar; Merck) should be used in the prevention of prostate cancer (PCa) due to unfavorable risk/benefit profiles, according to the FDA Oncologic Drugs Advisory Committee. The FDA often follows the recommendations of its advisory committees, but is not bound to do so.
Committee members yesterday voted overwhelmingly against recommending to expand the indication of the two drugs, both of which are currently approved as treatments for benign prostatic hyperplasia (BPH). The supplemental new Drug Application (sNDA) for Avodart was turned down by the advisory committee in a vote of 14-2 (with two abstentions); the Proscar vote came in at 17-0 against approval, with one abstention. Both drugs have been associated with an increase in aggressive tumors.
The proposed indication that was being sought by GSK for Avodart Soft Gelatin Capsules is for the reduction in the risk of prostate cancer in men who are at increased risk of developing the disease, based on findings from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. In this research, the agent provided a statistically significant reduction in the cumulative incidence of biopsy-proven prostate cancer after 4 years. (www.fda.gov/AdvisoryCommittees/Calendar/ucm230653.htm). However, this risk reduction was limited to the decrease in the incidence of low-risk prostate cancers, and a notable increase in high-grade tumors was detected. (www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM234934.pdf).
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In a statement yesterday, GSK’s Anne Phillips, MD, of the company’s oncology and research development division, expressed “disappointment” in the FDA committee’s conclusions, but affirmed that GSK would continue to work with the agency on the review of the sNDA (www.gsk.com/media/pressreleases/2010/2010_us_pressrelease_10103.htm).
Although Merck had no proposed indication for reduction of prostate-cancer risk with Proscar Tablets, the company was seeking to include the results of the Prostate Cancer Prevention Trial in the clinical-studies section of the product labeling. The PCPT demonstrated a statistically significant reduction in the seven-year period prevalence of prostate cancer with finasteride treatment. But investigators also reported an imbalance in high Gleason-grade prostate cancers—indicating more aggressive cancers—in the finasteride treatment arm, compared with placebo.
