Denosumab: in the prevention of skeletal-related events in patients with bone metastases from solid tumours.

Denosumab, a fully human monoclonal antibody, binds to the receptor activator of nuclear factor-κB ligand (RANKL) and thereby inhibits RANKL-mediated bone resorption. In various individual countries, subcutaneous denosumab is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumours (featured indication), and/or for the treatment of postmenopausal osteoporosis and/or of cancer treatment-induced bone loss in prostate or breast cancer patients. In three, pivotal, double-blind, multinational trials in adult patients with cancer-related bone metastases (total n > 5700), including trials in patients with advanced breast or prostate cancer, subcutaneous denosumab (120 mg every 4 weeks) was shown to be noninferior to intravenous zoledronic acid (4 mg every 4 weeks), as determined by the median time to first on-study skeletal-related event (primary endpoint) at the time of the primary analysis (≈34 or 41 months). Denosumab treatment was superior to zoledronic acid in terms of the primary endpoint in two trials in patients with breast cancer or prostate cancer, based on secondary superiority analyses. In a third trial in patients with solid tumours excluding breast or prostate cancer, superiority of denosumab treatment versus zoledronic acid treatment was not demonstrated. The tolerability profile of denosumab was manageable in patients with bone metastases from solid tumours. Osteonecrosis of the jaw occurred in 1.8% and 1.3% of patients in the denosumab and zoledronic acid groups during the primary treatment phase; the incidence after approximately 4 additional months of denosumab treatment was 2.2%.