MedicalResearch.com Interview with:
Professor Michael Gnant, M.D., FASC
Director and Chairman
Department of Surgery
President, Austrian Breast&Colorectal Cancer Study Group
Head, Breast Health Center Vienna
Comprehensive Cancer Center Vienna
Medical University of Vienna – Department of Surgery
Medical Research: What is the background for this study? What are the main findings?
Response: The background of this presentation is as follows: For many years, we have seen intriguing – but also sometimes conflicting – results of trials using adjuvant bone-targeted therapy.
ABCSG-18 is a placebo-controlled trial of adjuvant denosumab 60mg twice yearly, and I have been able to present to you at this year’s ASCO meeting the dramatic reduction in clinical fractures which was the primary end point of the trial. We have also showed that twice yearly denosumab can be administered without added toxicity in this double-blind placebo-controlled trial. These results were as well published in the Lancet earlier this year.
The obvious question remaining now is whether adjuvant treatment with the anti-RANK ligand antibody also improves outcomes in a way similar to what bisphosphonates do.
Main findings of ABCSG-18: disease-free survival results of the intention-to-treat analysis: In the placebo group, we observed 203 DFS events. In the denosumab group, there were 167 DFS events, resulting in a hazard ratio of 0.816, indicating an 18% relative DFS improvement by denosumab. In terms of absolute differences, the benefit was 1.2% at 3 years, 2.1% at 5 years, and 3.1% at 7 years.
Medical Research: What should clinicians and patients take away from your report?
Response: it is fair to say that adjuvant denosumab yields at least comparable outcome effects as bisphosphonates.
In summary: These time-driven DFS analyses of ABCSG-18 indicate that adjuvant denosumab improves disease-free survival in postmenopausal patients with hormone-receptor positive breast cancer. The Hazard ratio is 0.82, with borderline statistical significance in the ITT analysis – however sensitivity analysis shows that the ITT assumption is actually conservative in terms of the true benefit.
Adjuvant denosumab given at this dose and schedule is safe – there was not measurable differenc between denosumab and placebo in terms of SAEs or AEs, and particularly not a single case of ONJ or atypical fracture.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: Personally, I believe that adjuvant denosumab should be offered to postmenopausal breast cancer patients on adjuvant AI therapy
2015 SABCS abstract:
Abstract 504: Adjuvant denosumab in breast cancer: Results from 3,425 postmenopausal patients of the ABCSG-18 trial
Professor Michael Gnant, M.D., FASC (2015). Adjuvant Denosumab Improves Disease Free Survival in Hormone Receptor Positive Breast Cancer