Adjuvant therapy with aromatase inhibitors is recommended for postmenopausal women with hormone receptor-positive (HR+) early stage breast cancer but is associated with decreased bone mineral density and an increased risk of fractures. Adjuvant treatment with the anti-receptor activator of nuclear factor-κB ligand (RANKL) antibody denosumab was shown to significantly reduce the time to first clinical fracture in the primary analysis of the ABCSG-18 phase III trial. Now, disease-free survival (DFS) results from this trial provide additional support for denosumab in this setting.
In the ABCSG-18 trial, women with early stage HR+ breast cancer received adjuvant denosumab (n = 1,711) or placebo (n = 1,709) together with aromatase inhibitors; 14.7% of patients in the placebo group crossed over to receive denosumab. Denosumab provided a DFS benefit over placebo: at 5 years, DFS was 89.2% (95% CI 87.6–90.8) versus 87.3% (85.7–89.0) with placebo, and at 8 years DFS was 80.6% (78.1–83.1) and 77.5% (74.8–80.2).
“The magnitude of the survival effect is comparable to that observed in trials of adjuvant bisphosphonates (which did not really show a reduction in fractures), and the monoclonal antibody has fewer adverse effects and provides better quality of life than bisphosphonates,” comments Michael Gnant.
The incidence of adverse events (AEs) was similar in both treatment arms: AEs of any grade were reported by 80.0% and 79.2% of women receiving denosumab and placebo, respectively, which were grade ≥3 AEs in 30.5% in both groups.
“I believe that every postmenopausal woman with HR+ breast cancer receiving adjuvant aromatase inhibitors should be offered this therapy that halves the risk of clinical fractures, provides a moderate but significant DFS benefit, and does not have notable adverse effects,” concludes Gnant, remarking: “These injections are reasonably affordable, compared with the cost of fracture treatment or other modern anticancer therapies.”
Gnant, M. et al. 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. 20, 339–351 (2019)
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Romero, D. Healthier bones and less recurrence with denosumab. Nat Rev Clin Oncol 16, 272 (2019). https://doi.org/10.1038/s41571-019-0197-1