Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: A randomized, placebo-controlled trial

Purpose To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer. Patients and Methods Women with bone metastases (N = 228) were randomly assigned to receive 4 mg zoledronic acid (n = 114) or placebo (n = 114) via 15-minute infusions every 4 weeks for 1 year. The primary efficacy end point was the skeletal-related event (SRE) rate ratio between treatment groups. An SRE was defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Secondary end points included percentage of patients with at least one SIRE, time-to-first SRE, and Andersen-Gill multiple-event analysis. Results The SIRE rate ratio at 1 year (excluding HCM and adjusted for prior fracture) was 0.61 (permutation test; P = .027), indicating that zoledronic acid reduced the rate of SRE by 39 % compared with placebo. The percentage of patients with at least one SIRE (excluding HCM) was significantly reduced by 20 % by zoledronic acid (29.8 % v 49.6 % for placebo; P = .003). Zoledronic acid significantly delayed time-to-first SIRE (median not reached v 364 days; Cox regression; P = .007) and reduced the risk of SREs by 41 % in multiple event analysis (risk ratio = 0.59; P = .019) compared with placebo. Zoledronic acid was well tolerated with a safety profile similar to placebo. No patient treated with zoledronic acid had grade 3 or 4 serum creatinine increase. Conclusion Zoledronic acid significantly reduced skeletal complications compared with placebo across multiple end points in Japanese women with bone metastases from breast cancer. (c) 2005 by American Society of Clinical Oncology.