NIAGARA FALLS, ONTARIO—Denosumab significantly delays the time to bone metastases in men who have non-metastatic castrate-resistant prostate cancer (CRPC) and a PSA doubling time (PSADT) of six months or less.
In a poster presentation at the Canadian Urological Association’s 68th annual meeting, Blair Egerdie, MD, and his colleagues showed that the median time to the development of bone metastases was 25.9 months for patients treated with denosumab compared with 18.7 months for placebo recipients, for a significant 23% risk reduction.
In addition, the median time to multiple or symptomatic bone metastases was 44.6 months for denosumab-treated patients compared with 30.6 months for placebo recipients, for a significant 30% risk reduction.
“We’re not preventing bone metastases with this group of patients, who are the riskiest of the risky in terms of bone metastases. Rather, we’re improving quality of life,” said Dr. Egerdie, a urologist at Urology Associates/Urology Medical Research in Kitchener, Ontario.
Denosumab is a human monoclonal antibody that inhibits osteoclast-mediated bone destruction. The new study confirms the findings of a previous study published in the Lancet (2012;379:39-46) showing that the medication delays time to bone metastases in patients with non-metastatic CRPC.
Dr. Egerdie’s group recruited and randomized men with non-metastatic CRPC who had a PSA level of 8.0 ng/mL or higher and PSADT of 10 months or less. Patients received either subcutaneous denosumab 120 mg once every four weeks or subcutaneous placebo 120 mg once every four weeks. The men also received calcium and vitamin D supplementation to promote bone health.
Of the 716 patients who were randomized to each arm, 427 in the denosumab arm and 419 in the placebo arm had a PSADT of six months or less. The researchers focused their analysis on these patients.
The men in the two groups had the same median age (73 years) and were generally similar with respect to other baseline characteristics, including median time from diagnosis to randomization (5.5 years for denosumab patients and 5.6 years for placebo patients), median number of years in the study (1.5 and 1.3 years, respectively), median PSA (12.3 and 12.5 ng/mL, respectively), and median PSADT (3.2 and 3.1 months, respectively). The proportions of men at each T stage also were similar.
The denosumab and placebo arms had similar proportions of patients who experienced adverse events (AEs). Serious AEs occurred in 44.9% of denosumab-treated patients and 42.0% of placebo recipients. The most common side effects were back pain, constipation, arthralgia, and peripheral edema.
Jaw osteonecrosis developed in 18 (4.3%) patients on denosumab and none of the placebo recipients. Hypocalcemia developed in 10 (2.4%) and two (0.5%) patients, respectively.