A less-frequent dosing schedule of a bone-modifying agent (BMA) for treatment of skeletal-related events related to metastatic breast cancer is noninferior to standard dosing, according to research published in JAMA Oncology.
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Approximately 73% of patients with metastatic breast carcinoma—as well as 68% of patients with prostate cancer and nearly all patients with multiple myeloma—experience bone involvement. BMAs, such as pamidronate and zoledronic acid, have been used in conjunction with the monoclonal antibody denosumab to decrease risk of skeletal-related events in patients with bone metastases. Current standard dosing schedules of these BMAs accentuate the risk of adverse events due to overexposure.
Numerous clinical trials have investigated a less-frequent scheduling of BMAs to assess optimal timing between dosing. One study in particular, the OPTIMIZE-2 randomized trial, assessed the efficacy of zoledronic acid and pamidronate in less-frequent doses for treating bone metastases from breast cancer. Researchers sampled 416 patients with skeletal-related events from breast cancer who previously received at least 9 doses of zoledronic acid and/or pamidronate. Patients were randomized to receive zoledronic acid (4 mg, intravenously) every 4-weeks or every 12-weeks for an additional year. The primary endpoint of the study was the proportion of patients with one or more skeletal-related events, and secondary endpoints included time to first skeletal-related event and skeletal morbidity rate. Researchers used a predefined noninferiority margin of 10% when comparing the two arms.
Results of the study showed that zoledronic acid every 12 weeks for an additional year was noninferior to zoledronic acid every 4 weeks for a proportion of patients experiencing a skeletal-related event. The proportional difference between the two zoledronic acid groups (1.2%) was well within the predetermined noninferiority margin. There was no statistically significant difference in safety profiles, bone markers, and skeletal morbidity rates between the two groups.
This finding may have a significant impact on current clinical practice for treatment of patients with bone metastases from breast cancer, the authors wrote. Less frequent dosing not only can minimize risk of adverse events but also may reduce treatment costs.
