Denosumab monotherapy versus bisphosphonate switching in breast cancer bone metastases: A real-world cohort study on skeletal events and safety.

Abstract

e13166 Background: In real-world clinical practice, the administration of denosumab frequently deviates from standardized clinical trial protocols. Common patterns include sequential combination with bisphosphonates and delayed initiation following bone metastasis diagnosis. However, their effects on patient outcomes, especially skeletal-related events (SREs), remain unclear. This study aimed to comprehensively explore these real-world usage patterns of denosumab in breast cancer patients with bone metastases. Methods: A retrospective analysis was performed on 340 breast cancer patients with bone metastases who started bone-modifying agent (BMA) treatment between January 2019 and June 2024. All patients received at least one dose of denosumab during BMA treatment and had no pre-treatment SREs. Patients were stratified into two cohorts: the bisphosphonate-and-denosumab switched group (n = 120) and the denosumab-only group (n = 220). The primary endpoint was time to the first on-study SRE. Secondary endpoints included the time to first and subsequent SREs (cumulative SREs), treatment-related adverse effects, and so on. Results: Compared to the switched-treatment group, the denosumab group had a trend towards delaying the first SRE incidence (17.3% in the denosumab group and 26.7% in the switched group) and significantly reduced the risk of cumulative SREs at the period of 36 months treatment period (P = 0.027). In the denosumab group, 6-month delay in treatment initiation post-diagnosis of bone metastasis was associated with an 8.9% increase in first SRE risk. The number of bone metastases (single vs. multiple), lesion location (weight - bearing vs. non - weight - bearing), and lesion type (osteolytic vs. osteoblastic) did not significantly affect the first SRE incidence. The main reasons for switching from bisphosphonates to denosumab were uncontrolled bone symptoms, radiological progression, and renal impairment. Regarding adverse events, the denosumab group had a 42.7% hypocalcemia rate vs. 55% in the switched-treatment group, 1.8% vs. 1.7% for osteonecrosis of the jaw, and 0% vs. 6.7% for renal impairment. Conclusions: In real-world settings, denosumab demonstrated superior efficacy and a favorable safety profile compared to bisphosphonate-and-denosumab switching in breast cancer patients with bone metastases. Early denosumab initiation after bone-metastasis diagnosis may lead to better clinical outcomes. These findings suggest that patients who receive denosumab promptly as the primary treatment for bone metastases may have greater benefits.