The patients’ baseline characteristics were balanced between the two study arms. In both study arms, 47% of the patients had breast cancer, 38% had prostate cancer, and 15% had multiple myeloma.
More patients receiving zoledronic acid every 4 weeks had dose delays (62%) than patients receiving zoledronic acid every 12 weeks (37%; P<.01). The median total zoledronic acid dose was 56 mg in patients treated every 4 weeks and 24 mg in those treated every 12 weeks.
No significant difference occurred in the proportion of patients with one or more SREs, which was 260 patients (29%) in the 4-week arm and 253 patients (29%) in the 12-week arm (P=.79). In addition, no significant difference occurred in the time to SRE between the two study arms (P=.60).
The proportion of patients with one or more SREs had no significant differences between disease types and between the two dosing schedules.
The skeletal morbidity rate, which measures the incidence of SREs per year, was the same (mean skeletal morbidity rate, 0.4) in both study arms (P=.75). Also, no differences were found in pain scores or performance status over time.
Rates of osteonecrosis of the jaw were 2% with zoledronic acid at every 4 weeks and 1% at every 12 weeks (P=.08). Renal dysfunction rates were 1.2% and 0.6%, respectively (P=.12).
Bone turnover markers were suppressed more with the dosing every 4 weeks than with every 12 weeks (P<.01). The study measured C-telopeptide, which correlates with N-telopeptide but is not influenced by diet or time of day. The assay for C-telopeptide is less variable and more reproducible than the current assay for N-telopeptide.
Analysis of C-telopeptide levels in 2,530 samples from 553 patients found that, from weeks 12 to 96, treatment every 4 weeks suppressed C-telopeptide levels more than treatment every 12 weeks (P<.01). This did not translate to a clinical difference.
The study concluded that administering zoledronic acid every 12 weeks is noninferior to administering the drug every 4 weeks. The authors have a cost analysis that is currently in progress.
In comments about this study, Jamie H. Von Roenn, MD, of ASCO, said, “The time is right to begin recommending this drug every 12 weeks instead of every 4.”
1. Amadori D, Aglietta M, Alessi B, et al. Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer (ZOOM): a phase 3, open-label, randomized, non-inferiority trial. Lancet Oncol. 2013;14(7):663-670.
2. Hortobagyi GN, Lipton A, Chew HK, et al. Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: Results of the OPTIMIZE-2 trial [abstrace LBA9500]. J Clin Oncol. 2014;32(suppl):5s.