Continuing benefit of zoledronic acid in preventing skeletal complications in patients with bone metastases.

PURPOSE: We previously reported the efficacy of zoledronic acid 4 mg versus placebo (every 3 weeks for 24 months) for the prevention of skeletal-related events (SREs) in men with advanced prostate cancer and bone metastases. We conducted several retrospective exploratory analyses to determine whether zoledronic acid has continuing efficacy during long-term treatment.

PATIENTS AND METHODS: This report included analysis of the occurrence of SREs during the extension phase only (months 16-24), analysis of skeletal complications excluding the first SRE at 15 months (core phase), and stratified analysis of patients by history of SREs before study entry.

RESULTS: Patients (N=422) were randomized to receive zoledronic acid 4 mg or placebo. For the 132 patients who entered the extension phase, zoledronic acid significantly delayed the onset of first SRE (P=.009) and decreased the risk of developing an SRE by 53% compared with placebo (P=.022). Among all 422 patients, zoledronic acid significantly reduced the incidence of a second on-study SRE (P=.017) and significantly delayed the median time to second SRE compared with placebo (P=.006) at 15 months. Among 144 patients (34%) with a history of SREs before study entry, zoledronic acid significantly reduced the skeletal morbidity rate by 65% (P=.036) and reduced the overall risk of developing an SRE by 40% (P=.028) compared with placebo at 24 months.

CONCLUSION: This analysis confirms our previously reported results and suggests that long-term treatment with zoledronic acid provides continuing clinical benefit in patients with advanced prostate cancer, even after the occurrence of SREs.