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Long-Term Outcomes of Adjuvant Denosumab in Breast Cancer

2022; Volume: 1; Issue: 12 Linguagem: Inglês

10.1056/evidoa2200162

2766-5526

Michael Gnant, Sophie Frantal, Georg Pfeiler, Guenther G. Steger, Daniel Egle, Richard Greil, Florian Fitzal, Viktor Wette, Marija Balić, Ferdinand Haslbauer, Elisabeth Melbinger‐Zeinitzer, Vesna Bjelic‐Radisic, Silvia Artner-Matuschek, Franz Kainberger, Magdalena Ritter, Gabriel Rinnerthaler, P. Sevelda, Jonas Bergh, Stephanie Strobl, Christoph Suppan, Christine Brunner, Christine Deutschmann, Simon Peter Gampenrieder, Hannes Fohler, R. Jakesz, Christian Fesl, Christian F. Singer,

Estrogen and related hormone effects

BACKGROUND: Adjuvant aromatase inhibitors increase osteoporosis and fractures in patients with hormone receptor–positive breast cancer. We have previously reported outcomes of the ABCSG-18 (study 18 from the Austrian Breast & Colorectal Cancer Study Group) trial showing that adjuvant anti–receptor activator of nuclear factor-κB ligand denosumab treatment counteracts these adverse effects and may improve outcomes. We report here the final long-term outcomes. METHODS: ABCSG-18 is a prospective, double-blind, placebo-controlled, phase 3 trial in which 3425 postmenopausal patients with early hormone receptor–positive breast cancer receiving aromatase inhibitor therapy were randomly assigned in 58 trial centers to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months. The primary end point was the time to first clinical fracture after randomization. Secondary disease outcome–related end points were disease-free survival (DFS), bone metastasis–free survival (BMFS), and overall survival (OS). RESULTS: For this final protocol-defined analysis, median follow-up is 8 years (interquartile range, 6 to 9.6 years). There were 309 versus 368 DFS events (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.97) in the denosumab versus the placebo group, respectively, resulting in an absolute 9-year DFS benefit of 3.5 percentage points (79.4 vs. 75.9%). Adjuvant denosumab improved BMFS by 2.5 percentage points (88.9 vs. 86.4%; hazard ratio, 0.81; 95% CI, 0.65 to 1.00) and OS by 1.0 percentage point (90.9 vs. 89.9%; hazard ratio, 0.80; 95% CI, 0.64 to 1.01). No new toxicities for this dose of adjuvant denosumab were observed. CONCLUSIONS: DFS, BMFS, and OS continued to show benefit in this final long-term analysis of ABCSG-18. There were no new toxicities. (Funded by Amgen; ClinicalTrials.gov number, NCT00556374.)