SAT-719 Real World Experience with Denosumab Discontinuation in Oncology Patients: A Study from a Tertiary Cancer Center

Abstract Disclosure: J. Yoon: None. Background: Denosumab is an approved antiresorptive agent used to manage metastatic bone disease in patients with solid cancers. Despite its proven therapeutic efficacy, concerns remain about potential adverse effects following its discontinuation, particularly the increased risk of skeletal-related events (SREs) and rebound phenomena. However, clinical evidence on this issue remains limited. In this study, we evaluated real-world risk of SREs and osteoporotic fractures after denosumab discontinuation in oncology patients. Methods: We retrospectively reviewed medical records of cancer patients who received denosumab 120 mg monthly for bone metastasis between October 2018 and November 2024 at Chonnam National University Hwasun Hospital. Patients still undergoing denosumab treatment, those treated for less than 6 months, and those with less than 6 months of follow-up after denosumab discontinuation were excluded. We assessed the incidence of SREs and osteoporotic fractures before, during, and after denosumab discontinuation. Additionally, the occurrence of osteonecrosis of the jaw (ONJ) during denosumab treatment were investigated. Results: Among 542 patients with solid cancers treated with denosumab for bone metastasis, 68 patients were included in the final analysis. The primary cancer types were prostate cancer (51.5%), breast cancer (45.6%), lung cancer (1.5%), and renal cell carcinoma (1.5%). The median duration of denosumab treatment was 19.0 months (interquartile range 9.5–29.9 months). The median time since denosumab discontinuation was 14.8 months (interquartile range 8.0–25.8 months). SREs occurred in 13.2% of patients before denosumab initiation, decreased to 2.9% during treatment, and increased to 8.8% after discontinuation. Osteoporotic fractures were observed in 4.4% of patients before denosumab treatment and decreased to 2.9% during therapy; no osteoporotic fractures were reported after denosumab discontinuation. ONJ was observed in 16.2% of patients during denosumab treatment, leading to treatment discontinuation. Conclusion: In patients with solid cancers and bone metastasis, denosumab cessation was associated with an increased incidence of SREs, which had previously been reduced by the treatment. However, osteoporotic fractures, such as multiple vertebral fractures commonly seen in osteoporotic patients after denosumab discontinuation, were not observed in this study. Based on these findings, subsequent treatments should be considered following denosumab discontinuation, at least, to mitigate the risk of SREs. Furthermore, the incidence of ONJ in clinical practice may be higher than expected, necessitating greater awareness and preventive strategies. Presentation: Saturday, July 12, 2025