ATLANTA, GA USA (UroToday) - The authors wanted to assess the effects of denosumab on development of multiple or symptomatic bone metastases. In a previously published global randomized controlled trial of men with non-metastatic castrate-resistant prostate cancer (CRPC) at high risk for developing bone metastases, denosumab increased bone metastasis-free survival (BMFS) by 4.2 months vs. placebo and significantly reduced the risk of developing bone metastasis by 16% (hazard ratio 0.84; 95% CI: 0.71, 0.98; P = 0.032).
One thousand four-hundred and thirty-two men with non-metastatic CRPC at high risk for developing bone metastasis (PSA ≥8.0 ng/mL ≤3 months prior to randomization and/or PSA doubling time ≤10 months) were randomized 1:1 to receive a subcutaneous injection of denosumab (120 mg) or placebo once every 4 weeks. Bone metastases were identified by bone scans and confirmed by X-ray, CT, or MRI using a blinded central reader.
The authors defined bone bone metastasis-free survival (BMFS) as the time to first bone metastasis or death from any cause, was the primary endpoint. Additional analyses evaluated the effect of denosumab on development of multiple or symptomatic bone metastases.
During the study, 605 of the 1,432 enrolled patients developed bone metastases during the primary blinded treatment phase, where 359 (59%) had more than one bone metastases at detection.
Denosumab significantly reduced the risk of developing multiple bone metastases by 24% (hazard ratio [95% CI] = 0.76 [0.62, 0.94]; P = 0.011) vs. placebo. The median time to development of multiple bone metastases was 40.8 months for the placebo group and was not reached for the denosumab group. Denosumab also significantly reduced the risk of developing multiple or symptomatic bone metastases by 25% (hazard ratio [95% CI] = 0.75 [0.62, 0.91]; P = 0.004) vs. placebo. The median time to multiple or symptomatic bone metastases was 37.0 months for the placebo group and 44.6 months for the denosumab group.
Presented by Matthew Smith, Fred Saad, Neal Shore, Stephane Oudard, Kurt Miller, Bertrand Tombal, Paul Sieber, Karim Fizazi, Peter Van Veldhuizen, Ronaldo Damião, Gavin Marx, Juan Morote, Amy Feng, Roger Dansey and Carsten Goessl at the American Urological Association (AUA) Annual Meeting - May 19 - 23, 2012 - Georgia World Congress Center - Atlanta, GA USA