The addition of denosumab to aromatase therapy results in a significant reduction in clinical fractures and yields benefits for disease-free survival in postmenopausal women with hormone receptor–positive, early-stage breast cancer.
In postmenopausal women with hormone receptor—positive, early-stage breast cancer receiving treatment with aromatase inhibitor therapy, the addition of denosumab results in a significant reduction in clinical fractures, according to results of a new study, which also found that the treatment yielded benefits for disease-free survival.
While aromatase inhibitor therapy is the standard of care for these patients due to its association with improved outcomes compared with tamofixen, it increases the risk of osteoporosis and fractures by decreasing estrogen production, which is associated with decreased quality of life and increased mortality.
“Bisphosphonates and denosumab have been shown to counteract this cancer treatment—induced bone loss and improve bone mineral density, but only denosumab significantly reduces clinical (and vertebral) fractures in postmenopausal patients with breast cancer treated with an aromatase inhibitor,” wrote the researchers.
Results from a median of 73 months of follow-up demonstrated that not only did denosumab significantly delay the time to first clinical fracture (hazard ratio [HR], 0.5), increase bone mineral density, and result in no additional toxicity, but also that disease-free survival was significantly improved compared with treatment with placebo.
At the end of the study period, disease-free survival events were observed in 287 (16%) of 1709 patients in the placebo group and 240 (14%) of the 1711 patients in the denosumab group. Results also showed that denosumab yielded a significant disease-free survival benefit (HR, 0.82) compared with placebo.
At 5 years, disease-free survival was 89.2% among patients receiving denosumab and 87.3% among patients receiving placebo.
The study included 3420 patients enrolled in 58 centers across Austria and Sweden who had completed their initial adjuvant treatment with either surgery, radiation, chemotherapy, or a combination and were receiving adjuvant aromatase inhibitors between December 28, 2006, and July 22, 2013. Patients were randomized to receive either denosumab 60 mg or placebo every 6 months.
“In subgroups of patients with different lead times of denosumab or placebo after aromatase inhibitor initiation, patients who started denosumab concomitantly or within 3 months after initiation of aromatase inhibitor therapy had a greater benefit from denosumab than did patients who started denosumab at 3 months or later after aromatase inhibitor treatment,” wrote the researchers.
Adverse events were similar between the denosumab and placebo groups (1367 vs 1339). The most common serious adverse events were osteoarthritis, meniscus injury, and cataract. There was 1 treatment-related death in the denosumab group.
Gnant M, Pfeiler G, Steger G, et al; Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(3):339-351. doi: 10.1016/S1470-2045(18)30862-3.