Denosumab could offer advantages over zoledronic acid in prostate cancer, researchers suggest
Denosumab could be used to prevent bone events in men with metastatic prostate cancer that is resistant to hormone treatment, new research suggests.
Researchers found that denosumab delayed the onset of skeletal-related events for longer than zoledronic acid treatment did, with a similar adverse events profile (see Panel). The study was funded by Amgen, denosumab’s manufacturer.
The researchers conclude that denosumab could offer a new treatment option for this patient population and eliminate the inconveniences that zoledronic acid presents, such as the need for intravenous administration and dose adjustments to prevent renal injury.
“These limitations do not apply to denosumab, which is given subcutaneously, has no effect on renal function and no need for renal monitoring, and is not known to be associated with acute phase reactions,” they say.
David Thomson, lead pharmacist for the Yorkshire Cancer Network, said denosumab’s practical advantages over zoledronic acid might make it a more convenient treatment option, but highlighted the need for patients to be prescribed adequate calcium and vitamin D to stave off hypocalcaemia.
“It is to be hoped that it can be argued to commissioners that these advantages [over zoledronic acid] balance the additional cost likely to be seen with the procurement of denosumab,” he said.
A National Institute for Health and Clinical Excellence appraisal is under way for the use of denosumab for this indication, Mr Thomson told PJ Online. However, the expected date of publication of NICE’s advice is unknown so, if denosumab’s licensed indications are extended, access decisions are likely to be made at a local level, he said.
“These decisions might be made more difficult given the knowledge that zoledronic acid is due to go off-patent in 2012,” he added.
The study was published online (25 February 2011) in The Lancet. Amgen was also responsible for the trial design, and collection and analysis of the data.
Study method and findings
Over 1,900 adults with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonates were randomised to receive either 120mg subcutaneous denosumab plus IV placebo (n=950) or 4mg IV zoledronic acid plus subcutaneous placebo (n=951) every four weeks until the first skeletal-related event occurred (median time 20.7 and 17.1 months, respectively).
Denosumab delayed time to first onset of skeletal-related event by 18 per cent (3.6 months) compared with zoledronic acid (95 per cent confidence interval 0.71–0.95, P=0.0002 for non-inferiority analysis; P=0.008 for superiority analysis).
Overall survival and disease progression did not differ between the treatment groups, and nor did the incidence of adverse events and serious adverse events.
Calcium deficiency occurred within the first six months of treatment in 68 per cent of the denosumab group and 56 per cent of the zoledronic acid group.
Citation: The Pharmaceutical Journal URI: 11069665
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