Continuing benefit of zoledronic acid for the prevention of skeletal complications in men with advanced prostate cancer

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4575 Background: We previously reported the efficacy and safety of 4 mg zoledronic acid (Zol) at 15 months compared with placebo in patients with bone metastases from prostate cancer (Saad et al. J Natl Cancer Inst. 2002;94:1458–1468). We report here the results of an exploratory analysis of the 15- to 24-month extension phase of this study to evaluate the benefit of Zol treatment beyond 15 months.Methods: Data were collected during months 15 to 24 for patients who chose to enter the 9-month extension phase. Endpoints included the percentage of patients with a skeletal-related event (SRE), time to first SRE, skeletal morbidity rate (SMR), and multiple event analysis using the method of Andersen and Gill. Results: Of 422 patients randomized to the 4-mg or placebo treatment arms, 147 completed the 15-month core phase, and 133 elected to enter the extension phase. Among these patients, multiple event analysis revealed a 53% reduction in the risk of developing an SRE for patients treated with 4 mg Zol compared with placebo (risk ratio = 0.467; 95% CI = 0.243, 0.897; P = .022). Additionally, only 19% of patients treated with 4 mg Zol had an SRE during the extension phase versus 38% of patients treated with placebo (P = .017). Time to first SRE was significantly extended in the 4–mg Zol group compared with placebo (P = .036), and mean SMR was reduced approximately 2-fold (0.42 for 4 mg Zol versus 0.88 for placebo; P = .016). Conclusions: This exploratory analysis suggests that long-term treatment with Zol provides significant and ongoing clinical benefit in patients with bone metastases from advanced prostate cancer. Considering that patients who have an SRE are also at higher risk for a subsequent SRE, this analysis suggests that patients should continue on bisphosphonate therapy even after they have an SRE. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp.