According to research published early online in the Lancet, administration of denosumab to men with prostate cancer can delay bone metastasis.
Because bone metastases have been reported to be a major cause of morbidity and mortality in men with prostate cancer, researchers performed a phase III double-blind trial to evaluate the effects of denosumab on bone-metastasis-free survival in men with castration-resistant prostate cancer, no evidence of bone metastases at baseline, and a high risk of progression (prostate-specific antigen [PSA] >/= 8.0 micrograms/L or PSA doubling time </= 10.0 months, or both). A total of 1432 patients were randomised to receive subcutaneous denosumab 120 mg (n= 716) or subcutaneous placebo (n=716) every 4 weeks. The primary endpoint was bone-metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause.
The following results were reported:
• Denosumab increased bone-metastasis-free survival by a median of 4.2 months compared with placebo (median 29.5 [95% CI 25.4—33.3] vs. 25.2 [22.2—29.5] months; hazard ratio [HR] 0.85, 0.73—0.98, p=0.028).
• Denosumab also delayed time to first bone metastasis (33.2 [29.5—38.0] vs. 29.5 [22.4—33.1] months; HR 0.84, 0.71—0.98, p=0.032).
• However, overall survival did not differ between groups (denosumab, 43.9 [40•1—not estimable] months vs. placebo, 44.8 [40.1—not estimable] months; HR 1.01, 0.85—1.20, p=0.91).
• Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia: 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo, and hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo.
The researchers conclude that use of denosumab provides a useful option for the prevention of bone metastasis in patients with castration resistant prostate cancer.
A related editorial has discussed the study and concludes: “The more immediate question is when should one consider introducing denosumab to the treatment of prostate cancer? The reported findings support its use as an alternative to zoledronic acid, but do not support its broad use as a preventive agent for bone metastases in prostate cancer.