Once-weekly (70 mg/m2) vs twice-weekly (56 mg/m2) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials

Philippe Moreau, Keith A. Stewart, Meletios Dimopoulos, David Siegel, Thierry Facon, James Berenson, Noopur Raje, Jesus G. Berdeja, Robert Z. Orlowski, Hui Yang, Haijun Ma, Zandra Klippel, Anita Zahlten-Kumeli, Khalid Mezzi, Karim Iskander, Maria Victoria Mateos

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Combination of carfilzomib with dexamethasone (Kd) is approved for use in relapsed and/or refractory multiple myeloma (RRMM), with carfilzomib administered twice weekly at 56 mg/m2 (Kd56 BIW) or once weekly at 70 mg/m2 (Kd70 QW). Post hoc cross-trial comparisons were performed to compare efficacy and safety profiles of Kd70 QW vs Kd56 BIW dosing schedules using data from three trials of patients with RRMM: A.R.R.O.W., CHAMPION-1, and ENDEAVOR. To select for comparable patient populations, side-by-side efficacy and safety comparisons were performed in subgroups of patients with 2-3 prior lines of therapy who were not refractory to bortezomib. The overall response rate (ORR) was 69.9% (95% confidence interval [CI], 61.7-77.2) for Kd70 QW and 72.4% (95% CI, 65.9-78.2) for Kd56 BIW. Median progression-free survival (PFS) was 12.1 months (95% CI, 8.4-14.3) for Kd70 QW and 14.5 months (95% CI, 10.2—not evaluable) for Kd56 BIW. Frequency of grade ≥ 3 adverse events (AEs) was 67.6% for Kd70 QW and 85.3% for Kd56 BIW. Regression analyses (adjusting for prognostic factors) of all patients in the trials who received Kd70 QW vs Kd56 BIW estimated a PFS hazard ratio of 0.91 (95% CI, 0.69-1.19; P =.47) and an ORR odds ratio of 1.12 (95% CI, 0.74-1.69; P =.61). These results suggest that Kd70 QW has a comparable efficacy profile compared with Kd56 BIW and represents a convenient and well-tolerated treatment for patients with RRMM.

Original languageEnglish (US)
Pages (from-to)2989-2996
Number of pages8
JournalCancer medicine
Volume9
Issue number9
DOIs
StatePublished - May 1 2020

Keywords

  • carfilzomib
  • dosing schedule
  • once-weekly
  • relapsed and/or refractory multiple myeloma

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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