Amgen just completed, with positive results, a three-year Phase 3 placebo-controlled trial which evaluated denosumab for the treatment of bone loss (reduction of bone mineral density –BMD) in men undergoing androgen deprivation therapy (ADT) for non-metastatic prostate cancer.

One of the more common and significant side effects of ADT is loss of BMD. This loss is responsible for significant numbers falls and bone fractures. The effects of the ADT compound the natural BMD loss resulting from aging.

In this study of more than 1,400 men, were treated with denosumab. The treatment produced statistically significantly greater increases in bone mineral density (BMD) at the lumbar spine (primary endpoint) and non-vertebral sites compared with placebo at multiple time points. These improvements, as experienced by the men taking denosumab, were consistent with those seen in other denosumab studies evaluating BMD in women with breast cancer receiving aromatase inhibitor therapy (which also produces BMD loss), and in post-menopausal women with low bone mass.

The actual results were rather dramatic. At the completion of the evaluation period, which lasted for 36 months, men who received denosumab experienced less than half the incidence of new vertebral fractures (a secondary endpoint) compared with those receiving placebo, a statistically significant finding. Additionally, the men in the denosumab arm had fewer non-vertebral fractures over the evaluation period.

The adverse negative side effects and incidences reported in the study were similar between the denosumab and placebo arms of the study. The adverse events across both treatment arms were arthralgia (joint pain), back pain, constipation, and pain in extremity. Serious adverse infectious events occurred in approximately 5 percent of men receiving placebo treatment as compared with approximately 6 percent of those receiving denosumab, not a significant difference.

“This pivotal study in men with prostate cancer demonstrated once again that denosumab increases BMD consistently at all sites measured. We are also excited by the reduction in vertebral fractures, which permits the conclusion that the increased BMD seen in patients receiving denosumab is associated with improved bone strength,” said Roger Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. “We are encouraged by the potential benefit this may represent to prostate cancer patients who are undergoing ADT for whom bone loss and fractures are serious and under-recognized complications of cancer treatment.”

This study did not compare denosumab against Zomata, the current standard of care for men on ADT who have experienced BMD loss.

On ADT, speak to your doctor about the possibility of adding denosumab to your regime.

Joel T Nowak, MA, MSW