In breast cancer patients with bone metastasis, less frequent infusion of zoledronic acid was as effective as the standard monthly dose, the randomized OPTIMIZE-2 study showed.
“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 the University of Texas MD Anderson Cancer Center, Houston, at the American Society of Clinical Oncology (ASCO) 2014 annual meeting.
Zoledronic acid 4 mg given every 3 months was as effective as infusions given every 3 to 4 weeks, which is the schedule approved by the US Food and Drug Administration.
OPTIMIZE-2 compared the 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 rate of skeletal-related events was 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 change from baseline in bone turnover markers, were also similar between the arms, and safety profiles were similar as well.
ASCO press briefing moderator 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.”
The data are important because there are no evidence-based guidelines for the optimal treatment schedule after 1 year of treatment.
Importantly, less frequent dosing seemed to ameliorate some of the safety concerns for bisphosphonates as a class. Like all agents in the class, “zoledronic acid has some safety concerns,” said Hortobagyi, indicating osteonecrosis of the jaw (ONJ), long-bone fractures (ie, atypical femoral fractures), and chronic kidney function impairment.
The less frequent dosing in this study was associated with fewer cases of ONJ (0 vs 2) and lower rates of renal impairment (7.9% vs 9.6%) compared with monthly dosing. No patients experienced long-bone fractures.
Since the study size was, in Hortobagyi’s terms, “relatively modest” and there were some “design limitations,” he said the findings should be “interpreted with caution.”
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. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract LBA9500.