Safety of extending dosing intervals of denosumab in adults with solid cancer and bone metastasis: a review

Background: Denosumab is approved to be given every 4 weeks for the prevention of skeletal-related events in adults with solid cancer and bone metastasis. Research has suggested that it is safe to be given every 12 weeks, improving patients' quality of life and alleviating capacity and financial issues for healthcare providers; a definitive answer is required to change policy. Aims: This study aimed to assess the safety of extending dosing intervals of denosumab in adults with solid cancer and bone metastasis. Methods: A rigorous systematic review was conducted, using multiple databases and grey literature. Language was restricted to English. Included studies were critically appraised and assessed for potential bias. Findings: Three studies were included, with a total of 950 participants: two randomised controlled trials (RCTs) and one retrospective cohort study. A narrative analysis found no significant difference between the 4-weekly and 12-weekly regimens in terms of safety, apart from a higher rate of hospitalisations associated with the shorter interval. Conclusion: Further RCTs with robust methodology are required to confirm the findings of this review. A large non-inferiority phase III trial is in progress, which should address this.