Every Six-Month versus Single-Dose Adjuvant Zoledronate in Early Breast Cancer

BACKGROUND: Three-year data from a randomized trial comparing a single zoledronate infusion with infusions every 6 months were previously reported showing that a single infusion was associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation at 3 years. We now report the trial's final, prespecified 5-year follow-up data. METHODS: Patients who were postmenopausal (either naturally or treatment induced) with early breast cancer were randomly assigned to receive a single infusion of zoledronate (4 mg intravenously) or an infusion every 6 months for 3 years. Final 5-year preplanned secondary outcomes included recurrence-free survival, bone metastasis-free survival, overall survival, confirmed osteonecrosis of the jaw, and fragility fracture rates. RESULTS: A total of 211 patients were randomly assigned to receive either a single infusion (n=107) or an infusion every 6 months (n=104). After 5 years of follow-up, there were no clearly apparent differences between the groups for recurrence-free survival (88.7% vs. 84.1%; hazard ratio, 0.71; 95% confidence interval CI, 0.34-1.51), bone metastasis-free survival (90.6% vs. 86.0%; hazard ratio, 0.68; 95% CI, 0.30-1.52), or overall survival (91.6% vs. 88.0%; hazard ratio, 0.79; 95% CI, 0.34-1.82) in the single-infusion group versus the group receiving infusions every 6 months, respectively. After 5 years of follow-up, there were no significant differences in the incidence of osteonecrosis of the jaw (0% vs. 0%) or fragility fractures (5% vs. 2%) in the single-infusion group versus the 6-monthly infusion group, respectively. CONCLUSIONS: At 3 years of follow-up, a single infusion of zoledronate had previously been shown to be associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation compared with treatment every 6 months. In the current analysis, extended to 5 years of follow-up, there was no clear evidence of a difference in survival outcomes between the treatment approaches. (Funded by the CURE Foundation, REthinking Clinical Trials Program at the Ottawa Hospital Research Institute, and the Ottawa Hospital Foundation and its generous donors. Participating sites also received accrual support from the Canadian Cancer Clinical Trials Network 3CTN.).