The FDA will discuss at its advisory panel meeting the license extension application for denosumab (Xgeva®) to include the treatment of men with castration-resistant prostate cancer (CRPC) at high risk of developing bone metastases. Amgen will present the results of the pivotal phase III '147 trial, which forms the basis for the proposed new indication. If approved, the drug would become the first therapy licensed to prevent or delay the spread of cancer to bone in men with CRPC. Denosumb is currently approved to prevent skeletal-related events (SREs) in men with advanced prostate cancer that has already spread to the bone.

Study '147 was a randomized, placebo-controlled, multicentre phase III study comparing denosumb to placebo in prolonging bone metastasis-free survival in 1432 men with CRPC, who had no bone metastases at baseline, but were at increased risk based on PSA criteria. The study enrolled patients with a PSA ≥8 ng/mL or PSA doubling time of ≤10 months. The primary analysis of the overall study population showed that denosumb reduced the risk for bone metastases or death by 15% and increased bone metastasis-free survival, by a median of 4.2 months (29.5 versus 25.2 months, respectively; p=0.028). In exploratory analyses of patients with PSA doubling time of ≤10 months (80% study population), denosumb prolonged median bone metastasis-free survival time by 6.0 months compared with placebo. In patients with PSA doubling time ≤6 months, denosumb prolonged median bone metastasis-free survival time by 7.2 months compared with placebo.