A press release from Amgen has reported that denosumab was more effective than Zometa® (zoledronic acid) for the prevention of bone complications in women with metastatic bone disease from breast cancer. These results were obtained in a large Phase III clinical trial comparing denosumab to Zometa for prevention of bone complications.

Denosumab is a fully human monoclonal antibody that specifically targets the receptor activator of nuclear factor kappa B ligand (RANKL), a key mediator of the resorptive phase of bone remodeling. Denosumab is being studied across a range of conditions, including osteoporosis, treatment-induced bone loss, rheumatoid arthritis, bone metastases, and multiple myeloma. A biologics license application (BLA) has recently been submitted to the U.S. Food and Drug Administration for denosumab to be used in the treatment and prevention of postmenopausal osteoporosis in women and treatment and prevention of bone loss among patients undergoing hormone ablation for breast or prostate cancer.

Previous studies have suggested that denosumab may be better than bisphosphonates in preventing bone loss and skeletal complications in women with breast cancer. To directly compare denosumab to Zometa among breast cancer patients with bone metastases, researchers conducted a Phase III clinical trial. The study enrolled more than 2,000 patients. Study participants were assigned to receive either denosumab or Zometa.

The objective of the study was to determine whether the occurrence of skeletal-related events differed between the two study groups. The bone complications that were evaluated were fracture, radiation to the bone, surgery to the bone, and spinal cord compression. The results of this study suggest that denosumab may be more effective than Zometa in the management of patients with bone metastases. Patients treated with denosumab remained free of bone complications longer than patients treated with Zometa.

Comments: Full results are expected to be presented at an upcoming medical meeting.

Reference: Amgen press release. Denosumab demonstrates superiority over Zometa in pivotal phase 3 head-to-head trial in breast cancer patients with bone metastases. Available at: http://wwwext.amgen.com/media/media_pr_detail.jsp?year=2009&releaseID=1305355. Accessed July 8, 2009.