Oncoprescribe Blog: Denosumab approved for bone metastases in solid tumors

November 29th, 2010

Denosumab (Xgeva) was approved by the FDA for the prevention of  Skeletal Related Events (SRE’s) in patients with bone metastases from solid tumors. Denosumab is a monoclonal antibody targeting a protein called RANKL (Receptor Activator for Nuclear Factor kappa B Ligand). RANKL also known as  ODF (osteoclast differentiation factor) is an important molecule necessary for maintaining bone homeostasis. Overproduction of RANKL leads to increased osteoclastic activity resulting in bone resorption. Accelerated bone resorption can not only result in osteoporosis, but has also been implicated in the development of tumor related bone metastases. Denosumab binds to RANKL negating the formation, function and survival of osteoclasts.

Two international randomized studies demonstrated the superiority of Denosumab over Zoledronic acid in patients  with bone metastases, secondary to Breast Cancer and Castrate Resistant Prostate Cancer. In a third study involving patients with other solid tumors with bone metastases, Denosumab was found to be non-inferior to Zoledronic acid.

Denosumab, a RANK ligand inhibitor is a welcome addition to IV bisphosphonates, Pamidronate (Aredia) and Zoledronic acid (Zometa).