PURPOSE: Zoledronic acid decreases the risk for skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases but its role earlier in the natural history of the disease is unknown.
This phase III study evaluated the efficacy and safety of earlier treatment with zoledronic acid in men with castration-sensitive metastatic prostate cancer.
PATIENTS AND METHODS: Men with castration-sensitive prostate cancer and bone metastases whose androgen-deprivation therapy was initiated within 6 months of study entry were randomly assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously every 4 weeks) or a placebo. After their disease progressed to castration-resistant status, all patients received open-label treatment with zoledronic acid. The primary end point was time to first SRE, defined as radiation to bone, clinical fracture, spinal cord compression, surgery to bone, or death as a result of prostate cancer. Target accrual was 680 patients. Primary analysis was planned after 470 SREs. The study was discontinued prematurely (645 patients; 299 SREs) after the corporate supporter withdrew study drug supply.
RESULTS: Early zoledronic acid was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the zoledronic acid group (95% CI, 24.2 to 40.3) and 29.8 months in the placebo group (95% CI, 25.3 to 37.2; hazard ratio, 0.97; 95% CI, 0 to 1.17; one-sided stratified log-rank P = .39). Overall survival was similar between the groups (hazard ratio, 0.88; 95% CI, 0.70 to 1.12; P = .29). Rates of adverse events were similar between the groups.
CONCLUSION: In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs.
Smith MR, Halabi S, Ryan CJ, Hussain A, Vogelzang N, Stadler W, Hauke RJ, Monk JP, Saylor P, Bhoopalam N, Saad F, Sanford B, Kelly WK, Morris M, Small EJ. Are you the author?
Matthew R. Smith and Philip Saylor, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben Sanford, Alliance Statistics and Data Center, Duke University Medical Center, Durham, NC; Charles J. Ryan and Eric J. Small, University of California at San Francisco, San Francisco, CA; Walter Stadler, University of Chicago; Nirmala Bhoopalam, Loyola University of Chicago, Chicago, IL; Arif Hussain, University of Maryland, Baltimore, MD; Nicholas Vogelzang, Nevada Cancer Research Foundation CCOP, Las Vegas, NV; Ralph J. Hauke, University of Nebraska, Omaha, NE; J. Paul Monk, Ohio State University, Columbus, OH; W. Kevin Kelly, Thomas Jefferson University, Philadelphia, PA; Michael Morris, Memorial Sloan-Kettering Cancer Center, New York, NY; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Canada.
Reference: J Clin Oncol. 2014 Mar 3. Epub ahead of print.