Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial

N. Raje, S. Vadhan-Raj, W. Willenbacher, E. Terpos, V. Hungria, A. Spencer, Y. Alexeeva, T. Facon, A. K. Stewart, A. Feng, A. Braun, A. Balakumaran, G. David Roodman

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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.

Original languageEnglish (US)
Article numbere378
JournalBlood Cancer Journal
Volume6
DOIs
StatePublished - Jan 8 2016

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zoledronic acid
Multiple Myeloma
Confidence Intervals
Survival
Lost to Follow-Up
Survival Analysis
Proportional Hazards Models
Neoplasm Metastasis
Bone and Bones
Denosumab

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial. / Raje, N.; Vadhan-Raj, S.; Willenbacher, W.; Terpos, E.; Hungria, V.; Spencer, A.; Alexeeva, Y.; Facon, T.; Stewart, A. K.; Feng, A.; Braun, A.; Balakumaran, A.; Roodman, G. David.

In: Blood Cancer Journal, Vol. 6, e378, 08.01.2016.

Research output: Contribution to journalArticle

Raje, N, Vadhan-Raj, S, Willenbacher, W, Terpos, E, Hungria, V, Spencer, A, Alexeeva, Y, Facon, T, Stewart, AK, Feng, A, Braun, A, Balakumaran, A & Roodman, GD 2016, 'Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial', Blood Cancer Journal, vol. 6, e378. https://doi.org/10.1038/bcj.2015.96
Raje, N. ; Vadhan-Raj, S. ; Willenbacher, W. ; Terpos, E. ; Hungria, V. ; Spencer, A. ; Alexeeva, Y. ; Facon, T. ; Stewart, A. K. ; Feng, A. ; Braun, A. ; Balakumaran, A. ; Roodman, G. David. / Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial. In: Blood Cancer Journal. 2016 ; Vol. 6.
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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.",
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