Denosumab reduced fracture incidence, increased BMD in ADT-treated prostate cancer

Men treated with androgen-deprivation therapy had fewer new vertebral fractures and increased bone mineral density at all sites.

Denosumab, a human monoclonal antibody, given twice per year reduced the risk for new vertebral fractures by 62% in men receiving androgen-deprivation therapy for prostate cancer, according to data from a randomized trial. In addition, denosumab improved bone mineral density at all skeletal sites.

“Currently, in the United States, about one-third of the estimated 2 million prostate cancer survivors receive androgen-deprivation therapy; it is a very commonly used treatment,” Matthew Smith, MD, PhD, director of genitourinary oncology at Massachusetts General Hospital, told HemOnc Today. “It has established benefits in cancer control in many settings, but has potential side effects including greater risk for osteoporosis and fractures.”

According to Smith, a lack of randomized trials for the treatment or prevention of fractures in men undergoing androgen-deprivation therapy for prostate cancer led he and his colleagues to conduct this double blind, multicenter study.

The study included 1,468 men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. Patients were randomly assigned subcutaneous denosumab 60 mg every six months (n=734) or placebo. According to the researchers, the primary endpoint was percentage change in bone mineral density at the lumbar spine at 24 months; secondary endpoints included percent change in bone mineral density at the femoral neck and total hip at 24 months and at all three sites at 36 months and incidence of vertebral fractures.

The results were published in The New England Journal of Medicine.

Increased bone density, reduced fractures

Bone mineral density at the lumbar spine increased in the denosumab group as early as one month and continued to increase until 36 months compared with placebo. At 24 months, bone mineral density at this site had increased by 5.6% in the denosumab group and decreased by 1.0% in the placebo group (P<.001). Compared with placebo, at 24 months denosumab was also associated with a 4.8 percentage point improvement in bone mineral density of the total hip, a 3.9 percentage point improvement at the femoral neck, a 5.5 percentage point improvement at the distal third of the radius and a 4.0 percentage point improvement of the whole body.

At 12, 24 and 36 months, denosumab was associated with reduced incidences of new vertebral fractures compared with placebo. At 36 months, patients assigned denosumab had a 62% reduction in new vertebral fracture incidence compared with placebo (95% CI, 0.19-0.38). Though not significant, fractures occurred in fewer patients in the denosumab group compared with placebo (5.2% vs. 7.2%). However, significantly fewer patients in the denosumab group experienced more than one fracture at any site compared with patients in the placebo group (0.7% vs. 2.5%; P=.006).

According to Smith, without previous data on therapies to prevent fracture risk in men with prostate cancer receiving androgen-deprivation therapy, the degree of benefit observed in bone density and fracture reduction compares with the best results reported with any drug in postmenopausal osteoporosis.

Adverse event rates were similar at about 87% for both groups. The rate of serious adverse events was 34.6% in the denosumab group and 30.6% in the placebo group.

“If denosumab is approved for use then we will have a therapeutic option that has been shown to prevent fractures and this will fill the unmet need for an effective therapy to prevent fractures in men receiving ADT,” Smith said.

Smith told HemOnc Today that denosumab is also currently being examined in ongoing studies to determine whether the drug can prevent and treat bone metastases in prostate cancer. – by Stacey L. Adams

Smith M. N Engl J Med. 2009;doi:10.1056/NEJMoa0809003