Denosumab

Denosumab is a fully human monoclonal IgG(2) antibody that binds to receptor activator of nuclear factor-κB ligand (RANKL) and inhibits bone resorption due to RANKL-mediated osteoclastogenesis. In Europe, subcutaneous denosumab is indicated for cancer treatment-induced bone loss in men with prostate cancer and in postmenopausal women with breast cancer. In a large (n= 1468), well designed, multinational, phase III trial in adult patients with prostate cancer who were receiving androgen-deprivation therapy, bone mineral density (BMD) at the lumbar spine was significantly improved from baseline after 24 (primary endpoint) and 36 months of treatment with subcutaneous denosumab (60 mg once every 6 months), relative to that with placebo. Moreover, the risk of new vertebral fracture was significantly reduced by 62% in the denosumab group compared with the placebo group. In breast cancer patients receiving aromatase inhibitor therapy (n =252), subcutaneous denosumab (60 mg once every 6 months) significantly improved BMD at the lumbar spine from baseline after 12 (primary endpoint) and 24 months of treatment relative to placebo in a pivotal phase III trial. There were significant improvements in BMD at all skeletal sites, including the lumbar spine, total hip, and femoral neck, after 24 and 36 months' denosumab treatment in prostate cancer patients and after 12 and 24 months' treatment in breast cancer patients. In general, these improvements occurred irrespective of baseline characteristics, including age, duration of hormone ablation therapy, and baseline BMD. Denosumab treatment was generally well tolerated for up to 24 months in breast cancer patients and for up to 36 months in prostate cancer patients.