Abstract PS1-11-24: Effectiveness of Initial Denosumab Versus Sequential Bisphosphonate-to-Denosumab Therapy in Preventing Skeletal-Related Events in Breast Cancer Patients With Bone Metastases: A Retrospective Single-Center Study

Abstract Background: Skeletal-related events (SREs)—including pathological fractures, spinal cord compression, radiation to bone, and bone surgery—significantly impair quality of life in breast cancer patients with bone metastases. Denosumab, a monoclonal antibody targeting RANKL, differs mechanistically from bisphosphonates and is not renally cleared, potentially offering clinical advantages. However, in clinical practice, an increasing number of patients transition from bisphosphonates to denosumab. The comparative efficacy and safety of sequential therapy versus initial denosumab therapy in SRE prevention remain unclear. Methods: This retrospective single-center study analyzed 165 breast cancer patients with radiologically confirmed bone metastases treated between January 2019 and April 2024. Patients were grouped by Bone-targeting agent (BTA) strategy: initial denosumab treatment (n=67) or sequential bisphosphonate-to-denosumab therapy (n=98). Patients treated before 2019 were excluded, as denosumab was approved in China in 2019. The primary endpoint was the 1-year SRE rate, with SRE defined as the time to first on-treatment SRE. Baseline clinical characteristics including tumor subtype, stage, visceral metastases, bone lesion burden, and systemic therapy history were analyzed. Kaplan-Meier methods estimated SRE-free survival, and Cox regression identified factors associated with SRE risk. Results: The median age at bone metastasis diagnosis was 54.7 years. Median intervals from initial breast cancer diagnosis to bone metastasis varied by stage: 30.9 months (stage I, n=5), 50.2 months (stage II, n=14), 44.8 months (stage III, n=11), and 29.8 months (stage IV, n=125). Follow-up durations were 22.5 months in the sequential therapy group versus 11.3 months in the initial denosumab group. The number of bisphosphonate and denosumab administrations in the sequential group was 10 and 8, respectively, while that in the initial denosumab group was 9. A higher proportion of patients in the initial denosumab group received ≥2 lines of treatment (P 0.001). The median time from bone metastasis confirmation to BTA initiation was 0.9 months in both groups. After BTA initiation, the 12-month cumulative SRE incidence was lower with initial denosumab (5.9%; 95% CI, 0–12.3%) than with sequential therapy (15.7%; 95% CI, 8.1–22.7%). Pathological fractures (46.4%) and bone radiotherapy (50.0%) accounted for most SREs. The median time to first SRE was not reached in either group.Univariate Cox regression showed that second-line systemic therapy was associated with an increased SRE risk (HR=2.651, P=0.021). The 1-year incidence of adverse events, including hypercalcemia and medication-related osteonecrosis of the jaw (MRONJ), was lower in the initial denosumab group. Conclusions: This single-center retrospective study demonstrates that initiating denosumab treatment is associated with a lower incidence and delayed SRE onset compared to sequential bisphosphonate-to-denosumab therapy in breast cancer patients with bone metastases, with fewer adverse events. Second-line systemic therapy was associated with an increased SRE risk. These findings support early initiation of denosumab as a preferred BTA strategy. Citation Format: J. Cao. Effectiveness of Initial Denosumab Versus Sequential Bisphosphonate-to-Denosumab Therapy in Preventing Skeletal-Related Events in Breast Cancer Patients With Bone Metastases: A Retrospective Single-Center Study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-24.