Longer dosing interval for zoledronic acid for bone metastases is no less effective than standard-dosing interval

Results from a large clinical trial show that patients with bone metastases from certain cancers can receive less frequent zoledronic acid without sacrificing efficacy.

The recent article in JAMA reporting the results of the clinical trial comparing 12-week versus 4-week dosing intervals of zoledronic acid for patients with bone metastases from breast cancer, prostate cancer, or multiple myeloma, is important for our daily practice. The trial showed that there was no significant difference in the incidence of skeletal-related events in the two dose schedules. (Himelstein AL, Foster JC Khatcheressian JL, et al. Effect of Longer-Interval Standard Dosing of Zoledronic Acid on Skeletal Events in Patients with Bone Metastases: A Randomized Clinical Trial JAMA 317 (1), 48-58. 2017 Jan 03.)

Also of relevance was that this longer dosing interval halves the risk of jaw osteonecrosis caused by zoledronic acid although this reduction did not reach statistical significance. While the incidence of this side effect is generally low at about 2% of all patients, those who have had patients with this devastating side-effect of this class of medicines, will be familiar with the negative impact it has on their quality of life. Any reduction of this side effect is to be welcomed. The ability to use this agent in this way in patients with borderline renal function, is also good news.

The trial

The trial was conducted at 269 academic and community sites around the USA, and involved 1,922 patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma, who had at least one site of bone involvement. Patients were randomly assigned to receive zoledronic acid infusions every four weeks or every 12 weeks for two years.

The results

Among the 795 patients who completed the study, 29.5% of the 4-week dosing group and 28.6% of the 12-week dosing group experienced at least one skeletal-related event within two years of randomization. The proportion of skeletal-related events did not vary significantly according to type of cancer. In addition, pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the two groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.

Implications for patients

Lee S Schwartzberg MD, FACP in The Practice Update, outlines a third scheduling strategy to which the study lends additional evidence, the “administration of ‘induction’ zoledronic acid Q4W for a period of a year followed by a switch to the Q12W schedule. Two randomized trials have previously shown the maintenance of effect with this approach. Such a strategy would address the ability to achieve full suppression of bone turnover early on when it could be postulated the effect is most needed, while Q12W dosing later would reduce cost, complications, and clinic visits”. http://www.practiceupdate.com/c/48193/2/1

According to  Dr David Eedes of ICON, the reduction in both potential side effects as well as the convenience for patients, not to mention the financial benefits of this approach, means that the findings of this study has the potential to improve the quality of life of our patients with bone metastases.