Role of denosumab in prostate cancer

Abstract

Prostate cancer is known to have a tissue tropism for bone. This tissue tropism coupled with the experience with androgen deprivation therapy (ADT) over the past decade has led to heightened awareness of bone complications. Osteopenia and subsequent skeletal-related events (SREs) are one of the more concerning repercussions of ADT along with cardiovascular sequelae. To combat this decrease in bone mineral density, several agents have been developed for bone protection. The largest experience is with bisphosphonates (BPs), but recently (2011) head to head trials have established the role of monoclonal antibodies, particularly in patients with prostate cancer bone metastasis. For patients initiating ADT, monthly denosumab increased bone mineral density, the time for occurrence of any bone metastasis and time for symptomatic bone metastasis. Denosumab is a fully human monoclonal antibody of the IgG(2) subtype that selectively binds and neutralizes receptor activator NF kappa B ligand (RANKL), inhibiting osteoclastogenesis and bone turnover. In vitro binding assays have shown high-affinity binding of denosumab and osteoprotegerin to both soluble and membrane-bound forms of human RANKL. As clinicians may be less familiar with this newer agent, we compiled this review to summarize denosumab's current clinical indications for bone stabilization and mechanism of reduction in tumor burden.