New agent shows superiority in preventing SREs in men with advanced PCa

March 10, 2011

The RANK Ligand inhibitor denosumab (Xgeva) significantly delays skeletal-related events (SREs) in men with prostate cancer and bone metastases, French researchers recently reported.

The RANK Ligand inhibitor denosumab (Xgeva) significantly delays skeletal-related events (SREs) in men with prostate cancer and bone metastases, French researchers recently reported.

The drug met its primary and secondary endpoints and demonstrated superiority over zoledronic acid (Zometa) in preventing skeletal-related events, according to the study authors, led by Karim Fizazi, MD, PhD, of the Institut Gustave-Roussy, Villejuif. Denosumab was approved by the FDA on Nov. 18, 2010 for the prevention of SREs in patients with bone metastases from solid tumors.

"Bone metastases represents a significant risk for advanced prostate cancer patients due to the potential for serious bone complications such as fracture and spinal cord compression," Dr. Fizazi said. "The results of this study show that Xgeva prevents these serious bone complications more effectively than Zometa without the requirement of intravenous infusion and without the need for dose adjustment for renal function."

The international, phase III, randomized, double-blind head-to-head trial involved 1,901 patients with a median age of 71 years who had bone metastases from castration-resistant prostate cancer. They were randomized in a one-to-one ratio to receive either denosumab, 120 mg subcutaneously every 4 weeks, or zoledronic acid, 4 mg intravenously in a 15-minute infusion every 4 weeks.

Denosumab was superior to zoledronic acid in significantly delaying the time to first on-study SRE (hazard ratio, 0.82; 95% CI: 0.71, 0.95; p=.008) with a median time to first on-study SRE of 20.7 months vs. 17.1 months for zoledronic acid. Denosumab was also superior in significantly delaying the development of multiple SREs (time to first and subsequent on-study SRE) (HR, 0.82; 95% CI: 0.71, 0.94; p=.008).

Overall rates of adverse events and serious adverse events were generally similar between the two arms.

Study results were published online in The Lancet (Feb. 24, 2011).