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Definition |
Denosumab is a fully human monoclonal antibody directed against RANKL (receptor activator of nuclear factor
κB ligand), a key mediator of osteoclast formation, function, and survival. In M0 CRPC, denosumab has been
associated with increased bone-metastasis-free survival compared to placebo (median benefit: 4.2 months,
HR: 0.85, P = 0.028). However, this benefit did not translate into a survival difference (43.9 compared
to 44.8 months, respectively). The practical impact of this finding remains under discussion. The efficacy and
safety of denosumab (n = 950) compared with zoledronic acid (n = 951) in patients with metastatic CRPC
was assessed in a phase III trial. Denosumab was superior to zoledronic acid in delaying or preventing SREs,
as shown by time to first on-study SRE (pathological fracture, radiation or surgery to bone, or spinal cord
compression) of 20.7 vs. 17.1 months, respectively (HR 0.82; P = 0.008). Both urinary NTX and BAP were
significantly suppressed in the denosumab arm compared with the zoledronic acid arm (p < 0.0001 for both).
However, these positive findings were not associated with any survival benefit.
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