Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Patients With Multiple Myeloma

Summary

The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid in the treatment of bone disease from multiple myeloma.

Timeline

Start

2012-05-17

Primary completion

2016-07-19

Completion

2019-03-29

Outcome

Met primary endpoint

registry analysis (non-inferiority test); Zoledronic Acid vs Denosumab; p = 0.010; Hazard Ratio (HR) 0.98 (95% CI 0.85 to 1.14); Cox proportional hazards model NCT01345019 ↗

release “positive data from the Phase 3 '482 study, the largest international multiple myeloma trial ever conducted. In this study, XGEVA ® (denosumab) met the primary endpoint” amgen.com ↗

release “met the primary endpoint, demonstrating non-inferiority to zoledronic acid in delaying the time to first on-study skeletal-related event (SRE) in patients with multiple myeloma” amgen.com ↗

release “Phase 3 '482 study, the largest international multiple myeloma trial ever conducted. The study met its primary endpoint” amgen.com ↗

release “In the '482 study, XGEVA successfully met the primary endpoint” amgen.com ↗

Publications

• Background Raje N, Roodman GD, Willenbacher W, Shimizu K, Garcia-Sanz R, Terpos E, Kennedy L, Sabatelli L, Intorcia M, Hechmati G. A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America. J Med Econ. 2018 May;21(5):525-536. doi: 10.1080/13696998.2018.1445634. Epub 2018 Mar 5.
• Background Raje N, Terpos E, Willenbacher W, Shimizu K, Garcia-Sanz R, Durie B, Legiec W, Krejci M, Laribi K, Zhu L, Cheng P, Warner D, Roodman GD. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018 Mar;19(3):370-381. doi: 10.1016/S1470-2045(18)30072-X. Epub 2018 Feb 9.
• Background Huang SY, Yoon SS, Shimizu K, Chng WJ, Chang CS, Wong RS, Gao S, Wang Y, Gordon SW, Glennane A, Min CK. Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis. Adv Ther. 2020 Jul;37(7):3404-3416. doi: 10.1007/s12325-020-01395-x. Epub 2020 Jun 10.
• Background Terpos E, Raje N, Croucher P, Garcia-Sanz R, Leleu X, Pasteiner W, Wang Y, Glennane A, Canon J, Pawlyn C. Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study. Blood Adv. 2021 Feb 9;5(3):725-736. doi: 10.1182/bloodadvances.2020002378.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Denosumab	Monoclonal antibody	120 mg	Subcutaneous
Comparator	Zoledronic acid	Other / unclassified	4 mg	Intravenous

Indications