1463P - Denosumab for the prevention of symptomatic skeletal events (SSEs) in patients with bone-metastatic breast cancer: A comparison with skeletal-relat...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Supportive Measures
Presenter Jean-Jacques Body
Citation Annals of Oncology (2016) 27 (6): 497-521. 10.1093/annonc/mdw390
Authors J. Body1, R. von Moos2, A. Lipton3, M. Martin4, I. Diel5, G. Steger6, K. Tonkin7, R. de Boer8, H. Radcliffe9, D. Niepel10, A.T. Stopeck11
  • 1Head Of Medicine - Geriatrics, CHU Brugmann (ULB), 1020 - Brussels/BE
  • 2Department Of Oncology/hematology, Kantonsspital Graubünden, Chur/CH
  • 3Department Of Medical Oncology And Hematology, Penn State Hershey Medical Center, Hershey/US
  • 4Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 5Gynäkologische Onkologie, SPGO Mannheim, Mannheim/DE
  • 6Department Of Internal Medicine, Medical University of Vienna, Vienna/AT
  • 7Medical Oncology, University of Alberta Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 8Department Of Medical Oncology, Royal Melbourne Hospital, Parkville/AU
  • 9Biostatistics, Amgen Ltd., Uxbridge/GB
  • 10Medical Development, Amgen (Europe) GmbH, Zug/CH
  • 11Department Of Medical Oncology, Stony Brook Cancer Center, Stony Brook/US



A randomised controlled phase 3 trial of patients with breast cancer and bone metastases demonstrated denosumab was superior to zoledronic acid in reducing bone complications (SREs, defined as pathological fracture, surgery or radiation to bone, or spinal cord compression) (Stopeck AT, et al. J Clin Oncol 2010;28:5132–39). Recently, a composite endpoint of SSEs (symptomatic fracture, surgery or radiation to bone, or spinal cord compression) has been introduced as an alternative measurement of clinically relevant skeletal morbidity.


Eligible patients had confirmed breast cancer, evidence of ≥1 bone metastasis and had received no prior intravenous (IV) bisphosphonates. Patients were randomised double-blind to subcutaneous (SC) denosumab 120mg/IV placebo or IV zoledronic acid 4mg (adjusted for creatinine clearance)/SC placebo every 4 weeks. Daily oral calcium and vitamin D supplements were recommended. This post-hoc SSE analysis of the patient population includes symptomatic pathologic fractures (per investigators' judgement), spinal cord compressions and the requirement for preventative or corrective surgery or palliative radiation to bone.


As previously reported, fewer patients who received denosumab than zoledronic acid had confirmed first and subsequent SREs (Table). Similarly, fewer patients who received denosumab versus zoledronic acid had confirmed first and subsequent symptomatic events (SSEs). The median (95% CI) estimate of time to first SSE for both denosumab and zoledronic acid was not reached (HR = 0.76 [0.61, 0.93] P 


Denosumab reduced the risk of skeletal events in patients with bone-metastatic breast cancer to a similar extent regardless of whether the endpoint was defined as SRE or SSE. The risk of developing first and subsequent SSEs was reduced by up to 27% when comparing denosumab with zoledronic acid.

Clinical trial identification


Legal entity responsible for the study





J-J. Body: Lecture and consulting fees for Amgen. R. von Moos: Advisory Board: Amgen, Bayer, GSK, Novartis & Roche Research Grant: Bayer. M. Martin: Advisory Boardwalk, Novartis & AMGEN; Research funding Novartis. G. Steger: Honoraria from Amgen; Travel support and honoraria from Novartis. R. de Boer: Received honorarium/speakers fees from Amgen Australia. H-S. Radcliffe, D. Niepel: Employee of Amgen and holds Amgen stock. A.T. Stopeck: Received honorarium/consulting: Amgen; consulting: Pfizer, Sandoz, Biomarin, Peregrine. All other authors have declared no conflicts of interest.