Denosumab for prevention of fractures in men receiving androgen deprivation therapy (ADT) for prostate cancer (PC)

Abstract

5056 Background: ADT increases bone resorption, reduces bone mineral density (BMD), and increases fracture risk. Previously, we reported that denosumab, a fully human monoclonal antibody against RANKL, increased BMD and reduced the incidence of vertebral fractures in men with PC on ADT. We now describe in further detail the effects of denosumab on fractures at other skeletal sites. Methods: Men receiving ADT for nonmetastatic PC were randomized to receive subcutaneous denosumab 60 mg every 6 months (n = 734) or placebo (n = 734), with daily calcium and vitamin D supplements for 3 years. Men < 70 years old were required to have low BMD or a history of osteoporotic fracture. The primary endpoint was percentage change in lumbar spine BMD at 24 months. Key secondary endpoints were subject incidence of new vertebral fractures and fractures at any site (excluding fractures from severe trauma or pathologic fractures) over 3 years. Here, we evaluate the frequency of all fractures and fractures at key osteoporotic sites. The planned sample size (N = 1226) provided power to differentiate effects of denosumab from placebo for the primary and key secondary endpoints. Results: As previously reported, denosumab reduced the incidence of new vertebral fractures by 62% (p = 0.006), fractures at any site by 28% (p = 0.10), and multiple fractures at any site by 72% (p = 0.006) over 3 years. In a post-hoc analysis, we found a consistent trend showing a positive effect of denosumab on nonvertebral fractures. The occurrence of any fractures (counting all fractures within a subject) over 3 years was lower with denosumab than placebo (43 vs 77, p < 0.01). The subject incidence of fractures at 6 high-risk sites (wrist, humerus, hip, pelvis, leg [excluding patella], and clavicle) was numerically lower with denosumab (15 vs 24 placebo; p = 0.12). Also, fewer subjects in the denosumab arm than in the placebo arm reported fractures at key osteoporotic sites (e.g., 2 for denosumab vs 10 for placebo at the radius). Overall rates of adverse events were balanced between treatment arms. Conclusions: Denosumab significantly reduced the incidence of new vertebral fractures and in a post-hoc analysis, showed a trend toward a positive effect on nonvertebral fractures in men receiving ADT for nonmetastatic PC. [Table: see text]