Denosumab for the prevention of symptomatic skeletal events (SSEs) in patients with bone-metastatic breast cancer: A comparison with skeletal-related events (SREs)

Background

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.

Methods

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.

Results

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 

Conclusions

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

NCT00321464

Legal entity responsible for the study

Amgen

Funding

Amgen

Disclosure

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.