NEW YORK (Reuters Health) – Therapy with denosumab appears to augment bone mineral density and lower the risk of fracture among men with prostate cancer undergoing androgen-deprivation therapy, according to an article released early online by The New England Journal of Medicine.

“Androgen-deprivation therapy is the standard treatment for men with … prostate cancer; but many active men who have been successfully treated for their cancer develop debilitating bone fractures as a result,” lead investigator Dr. Matthew Smith commented in a prepared statement. Dr. Smith is affiliated with the Massachusetts General Hospital Cancer Center in Boston.

The Denosumab HALT Prostate Cancer Study, a prospective phase III trial conducted in North America and Europe, was designed to investigate the effects of denosumab, “a fully human monoclonal antibody against receptor activator of nuclear factor-kappa-B ligand,” which is a key mediator of osteoclast development.

The study originally included 1468 men (mean age 75 years) undergoing androgen-deprivation therapy for nonmetastatic, hormone-sensitive prostate cancer. However, only 62% completed the study. Withdrawal of consent, death, adverse events and disease progression were the primary reasons for withdrawal.

The men were randomly assigned in a double-blind manner to denosumab, 60 mg subcutaneously, or placebo every 6 months. Androgen deprivation therapy comprised bilateral orchiectomy or gonadotropin-releasing hormone agonist therapy.

As early as 1 month after the initial injections, significant differences in bone mineral density were found between the two groups at all measured sites. The differences continued to increase as compared with placebo (p < 0.001 at all measured time points) through 36 months, the study group reports. At 24 months, denosumab was associated with an increase in the bone mineral density of the lumbar spine of 5.6%, whereas the placebo group had lost 1.0% (p < 0.001). Similar patterns were documented for bone mineral density at the total hip, femoral neck, and distal third of the radius. The authors point out that denosumab’s effect at the distal third of the radius, “a site of predominantly cortical bone,” is of note because “neither bisphosphonates nor selective estrogen-receptor modulators have been reported to have a positive effect.” The study drug was also associated with decreases in the number of new vertebral fractures at 12, 24, and 36 months, the report indicates. At 36 months, cumulative incidence rates were 3.9% in the placebo group and 1.5% in the denosumab group (relative risk 0.38; p = 0.006). Subgroup analyses indicated that denosumab was just as effective in higher risk patients. Adverse events occurred at similar rates in the two groups. “The results of this study should be critically important in improving the quality of life of thousands of prostate cancer survivors,” Dr. Smith concluded. Reference:
N Engl J Med 2009;361.