title: Feasibility of extended dosing intervals of denosumab.
abstract: Purpose Denosumab is a crucial supportive care agent for patients with advanced cancers affecting the bone. Despite the importance of treatment, logistical and financial obstacles hinder the ability to maintain long-term adherence. This analysis was designed to provide preliminary data regarding the feasibility of extended denosumab dosing intervals. Methods This retrospective, case cohort study was conducted on patients receiving treatment with denosumab for malignancies with bone involvement. A total of 60 patients were identified for analysis and were divided into cohorts according to the average number of days between denosumab doses. The standard interval group was comprised of patients receiving treatment once every 27-30 days ( n = 29), whereas the deviated interval group was comprised of patients with an interval of 31-56 days between injections ( n = 31). The primary outcome was the percentage of patients developing a skeletal-related event. Secondary efficacy outcomes included rate of pathologic fracture, spinal cord compression, radiation therapy, surgery, and hypercalcemia. Results Patients in the deviated interval arm experienced significantly more skeletal-related events compared to the standard interval group (61% vs. 31%, respectively; p = 0.02). Secondary efficacy endpoints trended in favor of the standard therapy arm except for requirement for surgery (results were virtually equivalent) and hypercalcemia (no events in either group). Conclusions Non-adherence with the standard denosumab dosing schedule demonstrated an increased risk of experiencing a skeletal-related event. Preservation of denosumab dose density appears imperative to maintain efficacy and as such extending the dosing interval should be discouraged.
authors.affiliation: 1 Department of Pharmacy, University of Missouri Health Care, Columbia, MO, USA.|2 School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Kettle
authors.affiliation: 3 Department of Pharmacy, Froedtert and the Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Puja B
authors.initials: PB
authors.lastname: Patel
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy*; D000069448:Denosumab / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D050071:Bone Density Conservation Agents; D000069448:Denosumab
keywords: Denosumab; oncology; skeletal metastases