1580P - Pain Interference Outcomes in a Randomized Phase 3 Clinical Trial of Denosumab vs Zoledronic Acid (ZA) in Patients with Solid Tumors and Bone Metastases

Abstract

ABSTRACT Background In patients with advanced cancer, bone metastases cause pain and may lead to skeletal-related events (SREs). Subcutaneous (SC) denosumab prevented SREs more effectively than intravenous (IV) ZA in patients with solid tumors and bone metastases in a phase 3 clinical trial (n = 1597; Henry D, J Clin Oncol. 2010. Abstr 9133). We now describe pain interference outcomes for patients with solid tumors in this trial (ClinicalTrials.gov NCT00330759; May 25, 2006; sponsor Amgen Inc.). Methods Patients received 120 mg of denosumab SC or 4 mg of ZA IV every 4 weeks in a randomized, multinational, double-blind, double-dummy trial. Patient-reported pain interference (overall, activity, and affect) was assessed by the Brief Pain Inventory (0: does not interfere-10: completely interferes) at baseline (BL) and upon each monthly visit. Analyses included time to clinically meaningful (≥2-point increase or decrease from BL) worsening or improvement in pain interference, and percentage of patients reporting clinically meaningful worsening in pain interference by visit. Analyses were conducted for patients with no/mild pain (worst pain 0-4) at BL and all patients at risk. Results In patients with no/mild pain at BL, denosumab delayed the median time to clinically meaningful worsening in pain interference compared with ZA (overall 3.4 months, P = 0.0213; activity 1.8 months, P = 0.0124; affect 0.9 months, P = 0.0518). Similarly, fewer of these patients treated with denosumab vs ZA reported clinically meaningful worsening in pain interference over all visits (average relative difference: overall 13%; activity 16%; affect 10% fewer). Time to clinically meaningful improvement in pain interference was similar between treatment groups. Pain interference outcomes were similar among all patients at risk compared to those with no/mild pain at BL. Conclusion In patients with solid tumors, denosumab delayed time to worsening of pain interference, and fewer patients reported worsening in pain interference over time, compared with ZA. Greater effects on pain interference were seen for patients with no/mild pain at BL, suggesting the benefit of early intervention with denosumab. Disclosure C. Cleeland: Advisory board member for Amgen, Genentech, Merck, and Exelixis, L. Fallowfield: Consultancy honoraria for serving on an advisory board for Amgen Inc., R. von Moos: Advisory board member for Amgen, Roche, & Novartis and unrestricted research grants from Amgen and Roche, D. Patrick: Research funding from Amgen Inc., D.H. Henry: Advisory board member, served on the speakers bureau, and received research funding from Amgen Inc., V. Hirsh: Advisory board member for Amgen Inc., A. Feng: Employed by and owns stock/stock options in Amgen Inc., Z. Cong: Employed by and owns stock/stock options in Amgen Inc., A. Braun: Employed by and owns stock/stock options in Amgen Inc., All other authors have declared no conflicts of interest.