Utility of extended interval dosing of denosumab in patients with metastatic prostate cancer.

68 Background: Bone modifying agents, such as zoledronic acid and denosumab, are commonly used in patients (pts) with metastatic solid tumors to reduce the incidence of skeletal-related events (SREs). The FDA-approved administration schedule for both agents is every 4 weeks, however less frequent administration (i.e. every 12 weeks) is commonly observed in practice due to patient convenience. The efficacy and safety of these extended interval regimens is well-established for zoledronic acid, however there is little evidence available supporting this practice with denosumab. Methods: Pts with metastatic prostate cancer were evaluated for development of SREs during treatment with extended intervals of denosumab. 103 pts evaluated and treated at Indiana University Health between September 2019 and September 2024 were included in this analysis. A historical control group of pts receiving every 4-week dosing was used as comparison (1). SREs were defined as pathologic fracture, spinal cord compression, operation, or radiation to bone. Extended interval dosing is defined as an administration schedule >4 weeks apart on a consistent basis. Results: Median age at starting bone preserving agent was 70.6 years (range, 49.5-90). 24 pts (23.3%) had metastatic castration-sensitive prostate cancer and 79 pts (76.7%) had metastatic castration-resistant prostate cancer (mCRPC) at time of last follow-up. Incidence of SREs in all patients receiving extended interval denosumab was 23.3%. The incidence of SREs in patients with mCRPC receiving extended interval dosing was 26.6%. This compares favorably to historical data with incidence of SRE in the every 4 weeks dosing group at 35.9% (p=0.10). Median time to development of SRE was not estimable when all patients in the denosumab extended interval group were included in analysis. Median time to SRE in the mCRPC extended interval dosing group was 42.8 months and 20.7 months in the historical every 4-week dosing group (p<0.01). SREs identified for all patients receiving extended dosing interval denosumab were pathologic fracture (3, 2.9%), spinal cord compression (1, 1.0%), surgery (2, 1.9%), and radiation to bone (22, 21.4%). Conclusions: Our findings suggest that extended interval dosing of denosumab in patients with metastatic prostate cancer is not associated with an increased risk of development of SREs and may offer convenience for pts. Larger prospective studies are needed to validate these findings. 1. Fizazi K, Carducci M, Smith M, et al. Lancet 2011; 377: 813–822.