TY - JOUR
TI - Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial
AU - Raje, N.
AU - Vadhan-Raj, S.
AU - Willenbacher, W.
AU - Terpos, E.
AU - Hungria, V.
AU - Spencer, A.
AU - Alexeeva, Y.
AU - Facon, T.
AU - Stewart, A.K.
AU - Feng, A.
AU - Braun, A.
AU - Balakumaran, A.
AU - Roodman, G.D.
JO - Blood cancer journal
PY - 2016
VL - 6
TODO - null
SP - null
PB - Nature Publishing Group
SN - null
TODO - 10.1038/bcj.2015.96
TODO - 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
TODO - 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.
ER -