Ingo J Diel1, Jean-Jacques Body2, Alison T Stopeck3, Saroj Vadhan-Raj4, Andrew Spencer5, Günther Steger6, Roger von Moos7, François Goldwasser8, Amy Feng9, Ada Braun9. 1. Center for Gynecological Oncology, Mannheim, Germany. Electronic address: diel@spgo-mannheim.de. 2. Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles, Brussels, Belgium. 3. Department of Internal Medicine, Stony Brook Cancer Center, NY, USA. 4. MD Anderson Cancer Center, Houston, TX, USA. 5. The Alfred Hospital, Prahran, Victoria, Australia. 6. Medical University of Vienna, Vienna, Austria. 7. Kantonsspital Graubünden, Chur, Switzerland. 8. Teaching Hospital Cochin, Paris, France. 9. Amgen Inc., Thousand Oaks, CA, USA.
Abstract
BACKGROUND: We compared the activity of denosumab with zoledronic acid for delaying or preventing hypercalcaemia of malignancy (HCM) in patients with advanced cancer and bone metastases or with multiple myeloma. METHODS: Patient-level data were combined from two identically designed, randomised, double-blind, active-controlled, phase III trials of advanced cancer patients with breast cancer and other solid tumours (excluding breast or prostate cancer) or multiple myeloma. End-points included time to first on-study HCM, time to first and subsequent on-study HCM, proportion of patients experiencing HCM and proportion of patients experiencing recurrent HCM. RESULTS:Denosumab significantly delayed the time to first on-study HCM, representing a 37% reduction in the hazard ratio (HR) compared with zoledronic acid (HR, 0.63; 95% confidence interval (CI): 0.41-0.98; P = 0.042) and reduced the risk of developing recurrent HCM (time to first and subsequent on-study HCM) by 52% (rate ratio, 0.48; 95% CI: 0.29-0.81; P = 0.006). The median time on study was 12.9 months. Fewer patients receiving denosumab compared with zoledronic acid experienced an HCM event (1.7% versus 2.7%; P = 0.028). Of the 84 patients experiencing an HCM event, 40% of those receivingzoledronic acid experienced >1 event of HCM compared with 31% of those receiving denosumab. CONCLUSION:Denosumab treatment was more efficacious than treatment with zoledronic acid in delaying or preventing HCM in advanced cancer patients with breast cancer, other solid tumours or multiple myeloma.
RCT Entities:
BACKGROUND: We compared the activity of denosumab with zoledronic acid for delaying or preventing hypercalcaemia of malignancy (HCM) in patients with advanced cancer and bone metastases or with multiple myeloma. METHODS:Patient-level data were combined from two identically designed, randomised, double-blind, active-controlled, phase III trials of advanced cancerpatients with breast cancer and other solid tumours (excluding breast or prostate cancer) or multiple myeloma. End-points included time to first on-study HCM, time to first and subsequent on-study HCM, proportion of patients experiencing HCM and proportion of patients experiencing recurrent HCM. RESULTS:Denosumab significantly delayed the time to first on-study HCM, representing a 37% reduction in the hazard ratio (HR) compared with zoledronic acid (HR, 0.63; 95% confidence interval (CI): 0.41-0.98; P = 0.042) and reduced the risk of developing recurrent HCM (time to first and subsequent on-study HCM) by 52% (rate ratio, 0.48; 95% CI: 0.29-0.81; P = 0.006). The median time on study was 12.9 months. Fewer patients receiving denosumab compared with zoledronic acid experienced an HCM event (1.7% versus 2.7%; P = 0.028). Of the 84 patients experiencing an HCM event, 40% of those receiving zoledronic acid experienced >1 event of HCM compared with 31% of those receiving denosumab. CONCLUSION:Denosumab treatment was more efficacious than treatment with zoledronic acid in delaying or preventing HCM in advanced cancerpatients with breast cancer, other solid tumours or multiple myeloma.
Authors: Brent O'Carrigan; Matthew Hf Wong; Melina L Willson; Martin R Stockler; Nick Pavlakis; Annabel Goodwin Journal: Cochrane Database Syst Rev Date: 2017-10-30
Authors: Elizabeth S Ring; Michelle A Lawson; John A Snowden; Ingrid Jolley; Andrew D Chantry Journal: Calcif Tissue Int Date: 2017-11-02 Impact factor: 4.333