Denosumab delays time to bone metastasis in patients with hormone refractory non-metastatic prostate cancer who are at high risk of bone metastasis
Bony metastases in advanced prostate cancer are the cause of pain and significant morbidity including pathologic fracture and spinal cord compression. Denosumab is an osteoclast inhibitor that in this randomized study of 1432 men with non-metastatic hormone resistant prostate cancer was proven to significantly prolong bone metastasis-free survival by 4.2 months (29.5 v 25 placebo) and delay the time to first bone metastasis, 33.2 v 29.5 months. Overall survival did not change. In the denosumab group the rate of osteonecrosis of the jaw was 5% (v 0%) and hypocalcemia 2% (v <1%). 120 mg of denosumab was given subcutaneously every 4 week with vitamin C and D supplements. The patients were median 74 years old, median PSA 12.5 and had been on hormone therapy for median 47 months with good performance status. The discontinuation rate of 11% was the same in both groups, and side effects were back pain, constipation, arthralgia, diarrhea and were similar across the groups.