Abstract| Volume 48, SUPPLEMENT 4, S8, April 2012

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AOS13 Denosumab versus zoledronic acid for the prevention of skeletal-related events in patients with bone metastases secondary to solid tumours: An integrated analysis of three phase 3 studies

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      Skeletal-related events (SREs) cause significant morbidity in patients with solid tumours and bone metastases (BMs). An ad hoc analysis was undertaken to compare the effect of denosumab with zoledronic acid (ZA) in the prevention of SREs in patients with BMs secondary to solid tumours who participated in the denosumab pivotal phase 3 studies.


      Patients with breast cancer (N = 2046), prostate cancer (N = 1901), or other solid tumours (N = 1597) and BMs were randomly assigned in a 1:1 ratio to receive subcutaneous denosumab 120 mg or IV ZA 4 mg (adjusted for renal function) every 4 weeks. Patient-level data from three identically designed, double-blind, double-dummy studies were combined. Time to first on-study SRE and time to first and subsequent SREs were analysed using the Cox proportional hazards model and Anderson–Gill method, respectively.


      Patients received denosumab (N = 2776) or ZA (N = 2768). Denosumab was superior to ZA in delaying time to first on-study SRE and time to first and subsequent SREs. Denosumab reduced the risk of a first SRE by 18% compared with ZA (HR 0.82 [95% confidence interval (CI): 0.75, 0.89], p < 0.0001), reflecting a delay in median time to first SRE of 8.2 months. Denosumab also reduced the risk of first and subsequent SREs by 19% (HR 0.81 [95% CI: 0.74, 0.88], p < 0.0001) compared with ZA. Disease progression and survival were similar between groups. Incidence of adverse events (96.2% of denosumab group and 96.7% of ZA group), serious adverse events (56.2% of denosumab group and 57.3% of ZA group), and osteonecrosis of the jaw (1.7% of denosumab and 1.3% of ZA; p = 0.18) were similar in both groups. Hypocalcaemia was more frequent with denosumab (9.5% versus 4.8% for ZA) and acute phase reactions (first 3 days) were more common with ZA (20.4% versus 8.7% for denosumab).


      This integrated analysis confirmed results from the individual studies; denosumab was superior to ZA in reducing the risk of both first and multiple SREs among patients with solid tumours and BMs.


      Amgen Inc.
      A.T. Stopeck is a consultant for Amgen and Novartis; G. Richardson has received honoraria and research funding from Amgen; S. Siena has no conflicts of interest to declare; A. Lipton is a member of the speakers’ bureau, is a consultant, has received research support from Amgen and Novartis, and has provided expert testimony for Novartis; J. Brown has received consultancy fees from Amgen and Novartis, and payment for lectures from Amgen, Novartis, and Bayer; K. Fizazi has participated in Advisory Boards for Amgen and Novartis; D. Henry is a member of the speakers’ bureau, has participated in research and advisory boards for Amgen and Johnson and Johnson; F. Saad is a consultant and has carried out research for Amgen and Novartis; C. Ke and A. Braun are employed by Amgen and own stock.
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