Prevention of Skeletal-Related Events With Extended-Interval Denosumab: A Review of the Literature

Objective: To review published clinical trial data related to efficacy and safety of administering denosumab at extended dosing intervals for prevention of skeletal-related events (SREs) in cancer patients. Data Sources: A literature search of PubMed was performed (January 2006 to February 2023) using the following search terms: denosumab, bone metastasis, bone lesions, and lytic lesions. Abstracts from conferences, article bibliographies, and product monographs were also reviewed. Study Selection and Data Extraction: Relevant English-language studies were considered. Data Synthesis: Early phase II denosumab trials included treatment arms that utilized extended-interval denosumab, and various retrospective reviews, meta-analyses, and prospective trials have included extended-interval regimens. Most recently, the ongoing randomized REDUSE trial is comparing the efficacy and safety of extended-interval denosumab to standard dosing. At this time, the best available data are restricted to small, randomized trials not designed to compare efficacy and safety of extended-interval denosumab to conventional dosing and did not use consistent endpoints. Furthermore, primary endpoints of available trials largely consisted of surrogate markers of efficacy that may not be reflective of clinical outcomes. Relevance to Patient Care and Clinical Practice: Historically, denosumab has been dosed at 4-week intervals for prevention of SREs. If efficacy is maintained, extending the dosing interval could potentially reduce toxicity, drug cost, and clinic visits compared to every 4-week dosing. Conclusions: At this time, data demonstrating efficacy and safety of extended-interval denosumab remain limited, and the results of the REDUSE trial are eagerly anticipated to help answer remaining questions.