A Lipton1, K Fizazi2, A T Stopeck3, D H Henry4, M R Smith5, N Shore6, M Martin7, S Vadhan-Raj8, J E Brown9, G E Richardson10, F Saad11, D A Yardley12, K Zhou13, A Balakumaran13, A Braun13. 1. Division of Oncology, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, USA. Electronic address: alipton@hmc.psu.edu. 2. Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Villejuif, France. 3. Stony Brook Cancer Center, Stony Brook, USA. 4. Joan Karnell Cancer Center at Pennsylvania Hospital, Philadelphia, USA. 5. Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, USA. 6. Carolina Urologic Research Center, Myrtle Beach, USA. 7. Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain. 8. Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA. 9. Academic Unit of Clinical Oncology, University of Sheffield, Weston Park Hospital, Sheffield, UK. 10. Cabrini Medical Centre, Melbourne, Australia. 11. Departments of Surgery and Urology, University of Montreal Hospital Center, Montreal, Canada. 12. Sarah Cannon Research Institute and Tennessee Oncology, Nashville, USA. 13. Hematology/Oncology, Amgen Inc., Thousand Oaks, USA.
Abstract
BACKGROUND: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics. PATIENTS AND METHODS: Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type. RESULTS: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types. CONCLUSION:Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level.
RCT Entities:
BACKGROUND: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics. PATIENTS AND METHODS: Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type. RESULTS: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types. CONCLUSION:Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level.
Authors: Jeremy J Reynolds; Dominique A Rothenfluh; Nick Athanasou; Shaun Wilson; David C Kieser Journal: Eur Spine J Date: 2018-01-22 Impact factor: 3.134
Authors: G Mazziotti; A M Formenti; M B Panarotto; E Arvat; A Chiti; A Cuocolo; M E Dottorini; C Durante; L Agate; S Filetti; F Felicetti; A Filice; L Pace; T Pellegrino; M Rodari; M Salvatori; C Tranfaglia; A Versari; D Viola; S Frara; A Berruti; A Giustina; R Giubbini Journal: Endocrine Date: 2017-11-06 Impact factor: 3.633