SILVER SPRING, Md. – The majority of the Food and Drug Administration’s Oncologic Drugs Advisory Committee on Dec. 1 voted that the risk-benefit profile of finasteride and dutasteride, when used as chemopreventive agents for reducing the risk of prostate cancer, was not favorable.
In two separate studies comparing the two 5-alpha reductase inhibitors with placebo in thousands of men aged 50 years and older, the risk of being diagnosed with prostate cancer was significantly reduced among those randomized to the drug, compared with those on placebo. However, one of the main concern panelists cited was the increase in high grade prostate cancers diagnosed among the men in the treatment groups in both studies compared to those on placebo. The panel was not asked to vote on whether these drugs should be approved for preventing prostate cancer.
Dutasteride, marketed as Avodart by GlaxoSmithKline, was approved for treating benign prostatic hypertrophy (BPH) in 2001. Finasteride, marketed as Proscar by Merck, was approved for BPH in 1992 and is available in generic formulations. GSK filed for approval of the prevention indication in the United States and in Europe. Merck has proposed that the results of a prevention study be added to the finasteride label only. Currently, no drug is approved for prostate cancer prevention.
In a 7-year study of more than 18,000 men aged 55 years and older, considered at low to moderate risk of developing prostate cancer with a normal digital exam and a PSA of 3.0 ng/mL or less, the risk of being diagnosed with prostate cancer was reduced by 26% among those who received finasteride 5 mg a day, compared with those on placebo. In a 4-year study of 8,231 men aged 50 to 75 years considered at an increased risk of prostate cancer because of an elevated PSA (2.5–10 ng/mL) and one negative biopsy, the risk of being diagnosed with prostate cancer was reduced by 23% over 4 years among those on 0.5 mg of dutasteride, compared with those on placebo.
But in both studies, the reduction in the risk of prostate cancers was largely limited to low-grade cancers, and the rates of high-grade prostate cancers were higher among those on the 5-alpha reductase inhibitor, when compared with those on placebo.
In considering the risk-benefit profile of these drugs for chemoprevention, panelists also said they were concerned about how the drugs might be used by general practitioners and about the potential negative public health impact if used in the general population. Several also pointed out that the bar for approving a drug to prevent prostate cancer in otherwise healthy men should be set far higher than a drug used to treat a disease, and that there was a need for longer follow-up data.
The FDA usually follows the recommendations of its advisory panels, members of which have been cleared of conflicts related to the topic of the meeting. In some cases, panel members with a conflict are granted a waiver, but not at this meeting.