Zoledronic Acid Every 12 Weeks Noninferior to Every 4 Weeks

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No statistically significant difference was found in the time to first skeletal-related event between 4- and 12-week zoledronic acid treatments.
No statistically significant difference was found in the time to first skeletal-related event between 4- and 12-week zoledronic acid treatments.

In patients receiving monthly intravenous zoledronic acid and/or pamidronate disodium for 1 year or longer, continuing zoledronic acid for an additional year every 12 weeks was noninferior to zoledronic acid every 4 weeks, according to a study published in JAMA Oncology.1

Zoledronic acid is a potent bisphosphonate often given to patients with bone metastases to lower the risk of skeletal-related events; however, concerns have risen regarding its long-term monthly administration. Therefore, researchers sought to investigate the noninferiority of zoledronic acid every 12 weeks vs every 4 weeks in patients with metastatic breast cancer.

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For the multicenter, double-blind, phase 3 OPTIMIZE-2 trial (ClinicalTrials.gov Identifier: NCT00320710), investigators enrolled 406 women with bone metastases who had previously received a standard dosing regimen of zoledronic acid and/or pamidronate sodium. Participants were randomly assigned 1:1 to receive 4.0 mg of intravenous zoledronic acid every 4 or every 12 weeks with placebo for interim infusions for 1 year.

After 1-year of follow-up, results showed that 22.0% of patients in the zoledronic acid every 4 weeks group experienced a skeletal-related event compared with 23.2% in the zoledronic acid every 12 weeks group (noninferiority P =.02).

Researchers found that there was no statistically significant difference in the time to first skeletal-related event between treatment arms (hazard ratio, 1.06; 95% CI, 0.70-1.60; P =.79). There was also no significant difference in the mean skeletal morbidity rate between the 2 groups (P =.085). 

The safety profiles of the 2 arms were similar, with 95.5% of patients in the every 4 weeks group experiencing at least 1 adverse event vs 93.5% of those in the every 12 weeks group. 

The authors conclude that these findings may ultimately have a substantial impact on current clinical practice for treatment of patients with metastatic breast cancer and bone metastases. Further studies are necessary to evaluate the effect of long-term zoledronic acid treatment on bone saturation and bone retention rate in addition to clinically relevant outcomes.


1. Hortobagyi GN, Van Poznak C, Harker WG, et al. Continued treatment effect of zoledronic acid dosing every 12 vs 4 weeks in women with breast cancer metastatic to bone. JAMA Oncol. 2017 Jan 26. doi: 10.1001/jamaoncol.2016.6316. [Epub ahead of print]

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