@article{3101324,
    title = "Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial",
    author = "Raje, N. and Vadhan-Raj, S. and Willenbacher, W. and Terpos, E. and Hungria, V. and Spencer, A. and Alexeeva, Y. and Facon, T. and Stewart, A.K. and Feng, A. and Braun, A. and Balakumaran, A. and Roodman, G.D.",
    journal = "Blood cancer journal",
    year = "2016",
    volume = "6",
    publisher = "Nature Publishing Group",
    doi = "10.1038/bcj.2015.96",
    keywords = "albumin;  amino terminal telopeptide;  bortezomib;  clodronic acid;  cyclophosphamide;  denosumab;  lenalidomide;  melphalan;  proteasome inhibitor;  thalidomide;  zoledronic acid;  antineoplastic agent;  bisphosphonic acid derivative;  bone density conservation agent;  denosumab;  imidazole derivative;  zoledronic acid, adult;  Article;  bone metastasis;  cancer patient;  cancer survival;  controlled study;  double blind procedure;  drug efficacy;  drug withdrawal;  female;  follow up;  human;  hypercalcemia;  hypocalcemia;  jaw osteonecrosis;  major clinical study;  male;  middle aged;  multiple myeloma;  outcome assessment;  overall survival;  patient compliance;  phase 3 clinical trial;  randomized controlled trial;  side effect;  solid tumor;  stem cell transplantation;  survival rate;  aged;  autotransplantation;  Bone Neoplasms;  cancer staging;  clinical trial;  hematopoietic stem cell transplantation;  metastasis;  mortality;  multiple myeloma;  neoplasm;  pathology;  secondary;  treatment outcome, Aged;  Antineoplastic Combined Chemotherapy Protocols;  Bone Density Conservation Agents;  Bone Neoplasms;  Denosumab;  Diphosphonates;  Female;  Hematopoietic Stem Cell Transplantation;  Humans;  Imidazoles;  Male;  Middle Aged;  Multiple Myeloma;  Neoplasm Metastasis;  Neoplasm Staging;  Neoplasms;  Transplantation, Autologous;  Treatment Outcome",
    abstract = "In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P = 0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P = 0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P = 0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial. © 2016, Nature Publishing Group. All rights reserved."
}