Safety and efficacy of extended dosing intervals of denosumab in patients with solid cancers and bone metastases: a retrospective study.

AIM

More than half of patients with breast, lung, or prostate cancer who have bone metastases have evidence of skeletal-related events (SREs). Denosumab is a fully human monoclonal antibody that binds to and neutralizes receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts and their precursors. The United States Food and Drug Administration (FDA)-approved dose of denosumab is 120 mg every 4 weeks; however, other schedules have been used in practice for patient convenience. Evidence for the safety and efficacy of alternative dosing intervals is lacking.

PATIENT & METHODS: Adult patients with solid cancers and bone metastases who received at least two doses of denosumab 120 mg were reviewed. Patients were grouped based on an average denosumab dosing interval of <5 weeks (short-interval) 5-11 weeks (medium-interval) ⩾12 weeks (long-interval). The primary outcome was the time to first SRE while on denosumab between the short- and medium-interval groups. The secondary outcomes were overall survival (OS), efficacy comparisons between the other groups, and safety events.

RESULTS

There was no significant difference in median time to first SRE between the short- and medium-interval denosumab groups [33.2 28.4 months, hazard ratio (HR): 1.13, 95% confidence interval (CI): 0.66-1.92,  = 0.91] or the medium- and long-interval dosing groups (28.4 32.2 months, HR: 1.15, 95% CI: 0.66-2.01,  = 0.62). Median OS was not found to differ significantly between any of the groups. There were significantly more hospitalizations in the short-interval dosing group than the other groups (55.2% 33.8% 30.4%,  < 0.001).

CONCLUSION

Extending denosumab dosing intervals does not appear to negatively impact time to first SRE and is associated with fewer hospitalizations in real-world patients with solid cancers and bone metastases.