BoneKEy Reports | BoneKEy Watch

Denosumab delays bone metastasis in prostate cancer



DOI:10.1038/bonekey.2012.24

Denosumab is a fully human monoclonal antibody that binds to osteoblast-derived RANKL, inhibiting the activation of RANK-expressing osteoclasts. Denosumab reduces skeletal-related events in patients with solid tumours and bone metastases and has been used as a treatment in men with prostate cancer, where secondary bone tumours are a major cause of morbidity and mortality.

This study reports the findings of a phase 3, randomised, double-blinded and placebo-controlled trial that assessed the impact of monthly doses of denosumab on the occurrence of bone metastases in 1432 men with castration-resistant non-metastatic prostate cancer who were judged to be at high risk of future bone metastasis.

Men treated with 120 mg denosumab every 4 weeks (n=716) showed a significant increase in bone-metastasis-free survival; this increased by a median of 4.2 months compared to the control group (n=716). Denosumab treatment delayed the appearance of the first bone metastasis by an average of 3.7 months. Overall survival was similar in both groups, as were the rates of most adverse events. The treated group showed higher rates of jaw osteonecrosis (33 in the treated group, none in the placebo group) and hypocalcaemia (12 cf 2).

Editor's comment: Denosumab significantly delays the occurrence of bone metastasis in men with non-metastatic castration-resistant prostate cancer, who are at high risk of relapse, providing clinical evidence for the important role of RANKL signalling in the early development of skeletal lesions. This is also the first prospective study to demonstrate that ONJ incidence is increased in cancer patients treated with an antiresorptive vs placebo.


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