Agent markedly improves bone mineral density in androgen deprivation therapy-treated patients

Chicago-Twice-yearly injections of denosumab significantly improved bone mineral density (BMD) in men with prostate cancer treated with androgen deprivation therapy (ADT), according to findings from a study reported at the AUA annual meeting and published recently online in the New England Journal of Medicine (Aug. 11, 2009).

Patients treated with the investigational monoclonal antibody had 5% to 7% improvement in BMD compared with placebo treatment. The benefits remained consistent across a wide range of subgroup analyses.

"Denosumab increased BMD in all patient subgroups studied," said first author Matthew Smith, MD, PhD, associate professor of medicine at Harvard Medical School, Boston. "Patients who had higher baseline bone resorption seemed to get a greater treatment effect."

Investigators in the phase III, placebo-controlled clinical trial evaluated the ability of denosumab to prevent fracture in men with nonmetastatic prostate cancer treated with ADT. The primary finding was a 6.7% improvement in lumbar spine BMD at 24 months in the denosumab arm (p<.0001). Additionally, treatment with denosumab led to a 4.8% increase in total hip BMD and a 5.5% increase in the distal one-third radium BMD compared with placebo (p<.0001 for both comparisons).

The denosumab group had a 62% lower incidence of new vertebral fractures compared with placebo at 36 months (p=.006). The difference between groups reached statistical significance at 12 months and was maintained to the end of the study.

Dr. Smith presented results of a planned analysis that examined the effects of denosumab in various patient subgroups. The analysis included 1,468 men whose mean age was about 75 years. At entry, duration of ADT was about 20 months, mean lumbar spine BMD T-score was –0.41 to –0.31, mean total hip BMD T-score was –0.88 to –0.87, and median level of the bone turnover marker sCTx was 0.61 to 0.61ng/mL.

The subgroup analysis showed consistent statistically significant (p<.0001) improvement in BMD with respect to:

Support was provided by Amgen Inc., from which Dr. Smith receives consulting fees.