Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy

Summary

The purpose of this study is to determine whether denosumab compared to placebo, will reduce the rate of first clinical fracture in women with non-metastatic breast cancer receiving (non-steroidal) aromatase inhibitor therapy.

Timeline

Start

2006-12-18

Primary completion

2014-10-07

Completion

2022-07-26

Outcome

Met primary endpoint

registry Placebo vs Denosumab; p <0.0001; Hazard Ratio (HR) 0.504 (95% CI 0.39 to 0.65) NCT00556374 ↗

release “early hormone receptor positive (HR+) breast cancer receiving aromatase inhibitor therapy. The trial met its primary endpoint of time from randomization to first clinical fracture” amgen.com ↗

Publications

• Background Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger E, Bjelic-Radisic V, Artner-Matuschek S, Fitzal F, Marth C, Sevelda P, Mlineritsch B, Steger GG, Manfreda D, Exner R, Egle D, Bergh J, Kainberger F, Talbot S, Warner D, Fesl C, Singer CF; Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Aug 1;386(9992):433-43. doi: 10.1016/S0140-6736(15)60995-3. Epub 2015 May 31.
• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
• Gnant M, Frantal S, Pfeiler G, Steger GG, Egle D, Greil R, Fitzal F, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Artner-Matuschek S, Kainberger F, Ritter M, Rinnerthaler G, Sevelda P, Bergh J, Kacerovsky-Strobl S, Suppan C, Brunner C, Deutschmann C, Gampenrieder SP, Fohler H, Jakesz R, Fesl C, Singer C. Long-Term Outcomes of Adjuvant Denosumab in Breast Cancer. NEJM Evid. 2022 Dec;1(12):EVIDoa2200162. doi: 10.1056/EVIDoa2200162. Epub 2022 Nov 18.
• Minichsdorfer C, Fuereder T, Leutner M, Singer CF, Kacerovsky-Strobl S, Egle D, Greil R, Balic M, Fitzal F, Pfeiler G, Frantal S, Bartsch R, Gnant M. Effect of concomitant statin treatment in postmenopausal patients with hormone receptor-positive early-stage breast cancer receiving adjuvant denosumab or placebo: a post hoc analysis of ABCSG-18. ESMO Open. 2022 Apr;7(2):100426. doi: 10.1016/j.esmoop.2022.100426. Epub 2022 Mar 22.
• Gnant M, Pfeiler G, Steger GG, Egle D, Greil R, Fitzal F, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Jakesz R, Marth C, Sevelda P, Mlineritsch B, Exner R, Fesl C, Frantal S, Singer CF; 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 Mar;20(3):339-351. doi: 10.1016/S1470-2045(18)30862-3. Epub 2019 Feb 19.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Denosumab	Monoclonal antibody	60 mg	Subcutaneous
Subject	Zoledronic acid	Other / unclassified	5 mg	Intravenous
Background	Anastrazole	Unknown	—	—

Indications