Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials
Por:
Lipton, A, Fizazi, K, Stopeck, AT, Henry, DH, Brown, JE, Yardley, DA, Richardson, GE, Siena, S, Maroto, P, Clemens, M, Bilynskyy, B, Charu, V, Beuzeboc, P, Rader, M, Viniegra, M, Saad, F, Ke, CL, Braun, A, Jun, S
Publicada:
1 nov 2012
Resumen:
Background: Patients with bone metastases from advanced cancer often experience skeletal-related events (SRE), which cause substantial pain and morbidity. Denosumab, a fully human monoclonal antibody that inhibits RANK Ligand (RANKL), is a novel bone-targeted agent with a distinct mechanism of action relative to the bisphosphonate zoledronic acid, for prevention of SRE. This pre-planned analysis evaluates the efficacy and safety of denosumab versus zoledronic acid across three pivotal studies.
Methods: Patient-level data from three identically designed, randomised, double-blind, active-controlled, phase 3 trials of patients with breast cancer, prostate cancer, other solid tumours or multiple myeloma were combined. End-points included time to first SRE, time to first and subsequent (multiple) SRE, adverse events, time to disease progression and overall survival.
Findings: Denosumab was superior to zoledronic acid in delaying time to first on-study SRE by a median 8.21 months, reducing the risk of a first SRE by 17% (hazard ratio, 0.83 [95% confidence interval (CI): 0.76-0.90]; P < 0.001). Efficacy was demonstrated for first and multiple events and across patient subgroups (prior SRE status; age). Disease progression and overall survival were similar between the treatments. In contrast to zoledronic acid, denosumab did not require monitoring or dose modification/withholding based on renal status, and was not associated with acute-phase reactions. Hypocalcaemia was more common for denosumab. Osteonecrosis of the jaw occurred at a similar rate (P = 0.13).
Conclusion: Denosumab was superior to zoledronic acid in preventing SRE with favourable safety and convenience in patients with bone metastases from advanced cancer. (C) 2012 Elsevier Ltd. All rights reserved.
Filiaciones:
Lipton, A:
Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA
Fizazi, K:
Univ Paris Sud, Inst Gustave Roussy, Villejuif, France
Stopeck, AT:
Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA
Henry, DH:
Penn Hosp, Joan Karnell Canc Ctr, Philadelphia, PA 19107 USA
Brown, JE:
Canc Res UK Clin Ctr, Leeds, W Yorkshire, England
Yardley, DA:
Sarah Cannon Res Inst, Nashville, TN USA
Tennessee Oncol PLLC, Nashville, TN USA
Richardson, GE:
Cabrini Hosp, Malvern, Vic, Australia
Siena, S:
Osped Niguarda Ca Granda, Milan, Italy
Maroto, P:
Hosp La Santa Creu & St Pau, Barcelona, Spain
Clemens, M:
Klinikum Mutterhaus Borromaeerinnen, Trier, Germany
Bilynskyy, B:
Canc Treatment & Diagnost Ctr, Lvov, Ukraine
Charu, V:
Pacific Canc Med Ctr Inc, Anaheim, CA USA
Beuzeboc, P:
Inst Curie, Paris, France
Rader, M:
Nyack Hosp, Union State Bank Canc Ctr, Nyack, NY USA
Viniegra, M:
Corporac Med Gen San Martin, Buenos Aires, DF, Argentina
Saad, F:
Univ Montreal, Ctr Hosp, Montreal, PQ, Canada
Ke, CL:
Amgen Inc, Thousand Oaks, CA 91320 USA
Braun, A:
Amgen Inc, Thousand Oaks, CA 91320 USA
Jun, S:
Amgen Inc, Thousand Oaks, CA 91320 USA
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