Bone-Targeted Therapy for Hormone-Responsive Prostate Cancer

Robert Dreicer, MD, MS, FACP

Zoledronic acid did not reduce risk for skeletal events in men with castration-sensitive metastatic disease.

Zoledronic acid and denosumab are potent inhibitors of osteoclast-mediated bone resorption. Both are FDA approved to treat men with bone metastases from prostate cancer and disease progression despite androgen-deprivation therapy (ADT). They are also widely used to treat men with castration-sensitive metastatic prostate cancer. Given the potential toxicity burden and economic impact of these agents, industry- and NCI-funded Alliance investigators conducted a multicenter phase III study of zoledronic acid in the setting of castration-sensitive metastatic disease.

Patients treated with continuous ADT for metastatic prostate cancer for <6 months were randomized to receive intravenous zoledronic acid (4.0 mg or adjusted renal doses) or placebo every 4 weeks. The primary endpoint was time to first skeletal-related event (SRE). During an 8-year period, 645 patients were randomized when the corporate sponsor withdrew the supply of the study drug.

Of 621 eligible patients, the median time on study in the zoledronic and placebo groups was 11.8 and 13.6 months, respectively; the median time to first SRE was similar in these groups (31.9 and 29.8 months), as was survival (37.9 and 36.0 months). No major safety differences were observed.

Citation(s):

Smith MR et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (Alliance). J Clin Oncol 2014 Apr 10; 32:1143.