In patients with breast cancer and bone metastasis, less frequent infusion of zoledronic acid was as effective as the standard monthly dose in the randomized OPTIMIZE-2 study.
“We found that less frequent treatment may reduce the risk of serious side effects, with the additional benefits of reduced inconvenience to the patient and less cost,” said Gabriel N. Hortobagyi, MD, Professor of Medicine at M.D. Anderson Cancer Center, Houston, at ASCO 2014.
Zoledronic acid 4 mg given every 3 months was as effective as infusions given every 3 to 4 weeks, which is the FDA-approved schedule.
OPTIMIZE-2 compared the 2 schedules in 403 women with breast cancer and bone metastases who had received at least 9 doses of an intravenous bisphosphonate (either zoledronic acid or pamidronate) before enrolling in the study.
The rates of skeletal-related events were 22% in the monthly group and 23.2% in the every-12-week group, indicating that less frequent dosing is not inferior. Other efficacy measures, such as time to first skeletal-related event and bone turnover markers, were also similar between the 2 arms, as well as the safety profiles.
Patricia Ganz, MD, a supportive care specialist from the University of California, Los Angeles, commented, “It’s not necessary for women to come in every 4 weeks.”
These data are important, because there are no evidence-based guidelines for the optimal treatment schedule after 1 year of treatment.
Of note, less frequent dosing ameliorated some of the safety concerns for bisphosphonates as a class. Like all agents in the class, “zoledronic acid has some safety concerns,” said Dr Hortobagyi, indicating osteonecrosis of the jaw (ONJ), long-bone fractures (ie, atypical femoral fractures), and chronic kidney function impairment.
When compared with more frequent dosing, less frequent dosing in this study was associated with fewer cases of ONJ (0 vs 2, respectively) and lower rates of renal impairment (9.6% vs 7.9%, respectively). No patients experienced long-bone fractures.
Dr Hortobagyi advised that the findings should be “interpreted with caution,” because the study size was, in his terms, “relatively modest,” and there were some “design limitations.”