title: Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.
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.
authors.affiliation: Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Raje
authors.affiliation: University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vadhan-Raj
authors.affiliation: Internal Medicine V, Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Willenbacher
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Irmandade da Santa Casa de Misericordia de Sao Paulo, São Paulo, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Hungria
authors.affiliation: The Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Spencer
authors.affiliation: City Hospital No. 31, Saint Petersburg, Russia.
authors.forename: Y
authors.initials: Y
authors.lastname: Alexeeva
authors.affiliation: Hôpital Claude Huriez, Lille, France.
authors.forename: T
authors.initials: T
authors.lastname: Facon
authors.affiliation: Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Stewart
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Feng
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Braun
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Balakumaran
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Roodman
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D000069448:Denosumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000473:pathology; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid