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The monoclonal antibody denosumab prolongs metastasis free survival in men with hormone refractory prostate cancer. The study, presented at the 2011 European Multidisciplinary Cancer Congress (Stockholm, Sweden, September 23-27) found that the beneficial findings held across demographic and disease related subgroups.

Study presenter Prof Stéphane Oudard,  from the  Georges Pompidou Hospital, (Paris, France), said, “Our trial has shown that denosumab prolongs the period before metastasis where the patients’ quality of life has not yet suffered to a great extent. For the first time we’ve shown that targeting the bone micro-environment can work in this way.” Georges Pompidou Hospital, (Paris, France), said,

Up to 90 % of men with prostate cancer resistant to hormone treatment will have their primary tumour metastasise to the bone, placing the patient at risk for serious skeletal related events such as fractures and spinal cord compression.  Denosumab is a fully human monoclonal antibody that works by inhibiting RANKL, a protein known to be key to formation of osteoclasts. If the formation of osteoclasts can be impeded, said Oudard, the bone will remain strong and can continue to hold out against the development of metastases.

In the phase III  study, 1,432 patients with castrate resistant prostate cancer considered at high risk for bone metastasis (with high prostate specific antigen values and/or a short PSA doubling time)were randomised to denosumab 120 mg subcutaneously every four weeks (N=716) or placebo 120 mg subcutaneously every four weeks (n=716). The primary end point was time to first bone metastasis (symptomatic or asymptomatic) or death on study. Exclusion criteria included bone metastasis detected radiographically, metastatic involvement of distant organs and IV bisphosphonates.

The results show that bone metastasis free survival was 29.5 months in the group randomised to denosumab versus 25.2 months in the group receiving placebo (HR 0.85 95% CI 0.73,0.98; P=0.028).  The results held across subgroups related to age, region, race, Gleason scores and PSA stratum, with HRs ranging from 0.58 to 0.87. “Subgroup analysis showed that whatever the patient’s age, race, histology, or patient characteristics they all benefitted from denosumab,” said Oudard.

The trial showed that adverse effects were relatively similar between the denosumab and placebo groups with low blood calcium levels and osteonecrosis of the jaw being slightly more frequent in the denosumab group.

ECCO President Professor Michael Baumann said, “This is the first large clinical trial to demonstrate that targeting the bone microenvironment significantly delays onset of bone metastases in hormone resistant prostate cancer patient with high risk of development of bone metastases. What is really is really striking here is that the effect holds true for all sub-groups of patients evaluated.”

Reference:  S Oudard, M Smith, L Karsh et al. Denosumab  and Bone Metastasis-free Survival in Men with Castrate-resistant Prostate Cancer – subgroup Analyses from an international double-blind, randomised, phase 3 trial. Abstract 7003.

Conference: The 2011 European Multidisciplinary Cancer Congress