New findings point to the potential expanded benefit of denosumab therapy in the management of the breast cancer (BC) patient. The ABCSG (Austrian Breast-Colorectal Cancer Study Group)-18, a prospective, randomized, placebo-controlled, double-blind, multicenter, phase III trial, previously showed that adjuvant denosumab 60 mg twice yearly delayed time to first clinical fracture by 50% and increased bone mineral density (BMD) in postmenopausal women with early stage hormone receptor–positive (HR+) BC who were receiving aromatase inhibitor (AI) therapy. Denosumab’s effects are advantageous given that AIs decrease BMD and increase fracture risk.

The primary endpoint of ABCSG-18 was denosumab’s effect on bone, but a secondary endpoint was disease-free survival (DFS). DFS was defined as the time from randomization to the first evidence of local or distant metastasis, contralateral BC, secondary carcinoma, or death from any cause. (Other secondary endpoints included bone metastasis–free survival and overall survival but those results will not be available until after 2020.) Analysis of secondary endpoint data of this clinical trial, which included 3,420 women with early HR+ BC who were placed on denosumab 60 mg SC every 6 months, either at the start of or within 2 years of starting AI therapy, found that the antiresorptive agent may improve DFS while producing minimal adverse effects.

The median patient age was 64 years. AIs were started at randomization in 15.8% of patients, and the rest (84.2%) had previously started AI therapy. About one-quarter had undergone adjuvant or neoadjuvant chemotherapy and three-quarters had received adjuvant endocrine therapy.

The median duration of follow-up was 73 months, with 75.9% completing treatment according to protocol. Both intention-to-treat and sensitivity analyses were performed to address concerns about crossover bias.

DFS events occurred in 16.8% of the placebo group and 14.0% of the denusomab group. Denusomab was associated with a significant DFS benefit compared with placebo. DFS at 5 years was 89.2% in the denosumab group and 87.3% in placebo, and at 8 years DFS was 80.6% in the former and 77.5% in the latter group, respectively. The absolute difference in DFS was approximately 2% at 5 years and 3% at 8 years.

The number of treatment-emergent adverse effects was similar between the groups. A total of 6.1% of patients died—5.7% in the denosumab group and 6.4% in the placebo group. The cause of death from any BC occurred in 1.8% of the total study population. The study authors caution that despite the beneficial results associated with denosumab therapy, because of the descriptive nature of the analysis, the findings of this trial cannot be conclusive but only hypothesis-generating.

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