Denosumab (AMG 162) for Treatment of Breast Cancer with Bone Metastases

Receptor activator of NF-B ligand (RANKL) is a key mediator of osteoclast (bone dissolving cells) formation, function, and survival. Denosumab, a fully human monoclonal antibody, binds and inhibits RANKL, thus suppressing excess osteoclastic activity associated with bone metastases. In a phase II Study of denosumab versus standard IV bisphosphonate therapy, denosumab treatment resulted in rapid and sustained suppression of bone turnover and was at least as effective as IV BP at reducing the risk of skeletal related events (fractures, pain), with a safety profile similar to that seen in advanced breast cancer pts receiving cancer treatment. Adverse events (AE) among all pts included nausea, vomiting, asthenia, diarrhea, and bone pain. Osteonecrosis of the jaw (ONJ), a serious but uncommon complication of bisphosphonate therapy, ash not been observed with denosumab. Denosumab does not affect renal function. Bisphosphonate therapy may reduce renal function, so monitoring is required. Patients with renal dysfunction may not be able to receive bisphosphonates, or dose reductions are required.

CORT is conducting a randomized, double-blind study of denosumab versus IV zoledronic acid (Zometa) bisphosphonate therapy for treatment of metastatic breast cancer patients with bone metastases.

For more information on these studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.