Abstract
BACKGROUND: The purpose of this study was to evaluate the efficacy of denosumab or zoledronic acid (ZA) using symptomatic skeletal events (SSEs) as the primary endpoint in Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer. METHODS: Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer receiving subcutaneous denosumab 120 mg Q4W, or intravenous ZA 4 mg Q4W until the primary analysis cut-off date were retrospectively analysed in the Hong Kong Practice-Based Cancer Research Center(HKCRC) from March 2011 to March 2013. The time to first on-study SSE that was assessed either clinically or through routine radiographic scans was the primary endpoint. RESULTS: 242 patients received denosumab or ZA treatment (n = 120, mean age of 64.9 years (SD 3.01) and n = 122, 65.4 years (3.44), respectively). The median times to first on-study SSE were 14.7 months (12.9-45.6) and 11.7 months (9.9-45.6) for denosumab and ZA, respectively (hazard ratio, HR 0.44, 95% CI 0.71-2.95; p = 0·0002). Compared with the ZA group, denosumab-treated patients had a significantly delayed time to first SSE (HR 0.65 [95% CI 0.29-1.45], p < 0.0001). An increased incidence of SSE was found in the 16-month follow-up with rates of 2.1 and 10.7% for denosumab and ZA, respectively (P = 0.033). The difference persisted with time with rates of 8.3 and 17.2% at the final follow-up, respectively (P < 0.05). CONCLUSION: In postmenopausal women aged ≥60 years with oestrogen-receptor-positive advanced breast cancer, denosumab significantly reduced the risk of developing SSEs compared with ZA. The findings of this pilot trial justify a larger study to determine whether the result is more generally applicable to a broader population.