Less-Frequent Dosing of Zoledronic Acid Maintains Efficacy, Improves Safety for Myeloma Patients

Recent guidelines suggest that zoledronic acid – a third-generation aminobisphosphonate used to treat certain bone disease, including multiple myeloma (MM) – should be administered intravenously every three to four weeks to reduce the incidence of skeletal-related events and pain in patients with bone metastases. However, a randomized, open-label study published in JAMA found that the dosing frequency of zoledronic acid can be reduced to once every three months (rather than monthly), without increasing the risk of skeletal-related events. This dosing interval also may reduce adverse events (AEs) and decrease treatment costs, according to the researchers.

Andrew L. Himelstein, MD, from the Helen F. Graham Cancer Center & Research Institute in Newark, Delaware, and authors enrolled 1,822 patients (median age = 65 years) with breast cancer (n=855), prostate cancer (n=689), and MM (n=278) who had at least one site of bone involvement and had been treated at one of 269 academic and community sites in the United States between May 2009 and April 2012.

Patients were randomized to receive zoledronic acid intravenously every four weeks (n=911) or every 12 weeks (n=911) for two years. A total of 795 patients completed the study.

After two years, 260 patients (29.5%) in the once-monthly dosing group and 253 patients (28.6%) in the every-12-weeks dosing group experienced at least one skeletal-related event (the study’s primary endpoint; defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone; p<0.001 for non-inferiority). The skeletal morbidity rate (defined as the mean number of skeletal-related events) was 0.4 in both groups. Pain and performance status scores also were similar between both groups, the authors wrote.

However, patients in the every-12-weeks dosing group had better adherence to the treatment schedule than those in the once-monthly dosing group; 63 percent of patients in the less-frequent dosing group had no treatment delays, compared with 38 percent of the group taking the drug monthly.

Source: Himelstein AL, Foster JC, Khatcheressian JL, et al. Effect of longer-interval vs standard dosing of zoledronic acid on skeletal events in patients with bone metastases: a randomized clinical trial. JAMA. 2017;317:48-58.