The full data on the use of denosumab to delay the onset of bone metastasis in men with high-risk, progressive, non-metastatic, castration-resistant prostate cancer (CRPC) were published on line yesterday in The Lancet. We originally reported the results of this trial as presented at the annual meeting of the American Urological Association (AUA) in May this year.
The article by Smith et al. does not appear to provide any new information by comparison with the original data presented at the AUA. The major outstanding question is whether the U.S. Food & Drug Administration (FDA) will be willing to approve denosumab as an effective and safe treatment for the delay of onset of evident bone metastasis in men with non-metastatic CRPC. No drug has ever been approved for this indication.
There are no data to show that the delay in onset of bone metastasis in patients of this type is associated with a related prostate cancer-specific or all-cause survival benefit. In this trial, men in the denosumab arm of the study were taken off denosumab therapy when evident metastases could be observed. It is not known whether keeping these men on denosumab might have resulted in any form of survival benefit. Furthermore, it might be difficult to carry out a trial today that could isolate a survival benefit associated with denosumab given the effects of all the other approved and investigational therapies that are now being utilized in men with metastatic CRPC.
The FDA is expected to make a decision whether to approve denosumab for the prevention of evident bone metastases in men with non-metastatic CRPC on or before April 26, 2012.