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Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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

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/m(2) (Kd56 BIW) or once weekly at 70 mg/m(2) (Kd70 QW). Post hoc cross‐trial comparisons were performed to compare efficac...

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Autores principales: Moreau, Philippe, Stewart, Keith A., Dimopoulos, Meletios, Siegel, David, Facon, Thierry, Berenson, James, Raje, Noopur, Berdeja, Jesus G., Orlowski, Robert Z., Yang, Hui, Ma, Haijun, Klippel, Zandra, Zahlten‐Kumeli, Anita, Mezzi, Khalid, Iskander, Karim, Mateos, Maria‐Victoria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196059/
https://www.ncbi.nlm.nih.gov/pubmed/32108443
http://dx.doi.org/10.1002/cam4.2945
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author Moreau, Philippe
Stewart, Keith A.
Dimopoulos, Meletios
Siegel, David
Facon, Thierry
Berenson, James
Raje, Noopur
Berdeja, Jesus G.
Orlowski, Robert Z.
Yang, Hui
Ma, Haijun
Klippel, Zandra
Zahlten‐Kumeli, Anita
Mezzi, Khalid
Iskander, Karim
Mateos, Maria‐Victoria
author_facet Moreau, Philippe
Stewart, Keith A.
Dimopoulos, Meletios
Siegel, David
Facon, Thierry
Berenson, James
Raje, Noopur
Berdeja, Jesus G.
Orlowski, Robert Z.
Yang, Hui
Ma, Haijun
Klippel, Zandra
Zahlten‐Kumeli, Anita
Mezzi, Khalid
Iskander, Karim
Mateos, Maria‐Victoria
author_sort Moreau, Philippe
collection PubMed
description 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/m(2) (Kd56 BIW) or once weekly at 70 mg/m(2) (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.
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spelling pubmed-71960592020-05-04 Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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 Moreau, Philippe Stewart, Keith A. Dimopoulos, Meletios Siegel, David Facon, Thierry Berenson, James Raje, Noopur Berdeja, Jesus G. Orlowski, Robert Z. Yang, Hui Ma, Haijun Klippel, Zandra Zahlten‐Kumeli, Anita Mezzi, Khalid Iskander, Karim Mateos, Maria‐Victoria Cancer Med Clinical Cancer Research 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/m(2) (Kd56 BIW) or once weekly at 70 mg/m(2) (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. John Wiley and Sons Inc. 2020-02-28 /pmc/articles/PMC7196059/ /pubmed/32108443 http://dx.doi.org/10.1002/cam4.2945 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Moreau, Philippe
Stewart, Keith A.
Dimopoulos, Meletios
Siegel, David
Facon, Thierry
Berenson, James
Raje, Noopur
Berdeja, Jesus G.
Orlowski, Robert Z.
Yang, Hui
Ma, Haijun
Klippel, Zandra
Zahlten‐Kumeli, Anita
Mezzi, Khalid
Iskander, Karim
Mateos, Maria‐Victoria
Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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
title Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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
title_full Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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
title_fullStr Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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
title_full_unstemmed Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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
title_short Once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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
title_sort once‐weekly (70 mg/m(2)) vs twice‐weekly (56 mg/m(2)) 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
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196059/
https://www.ncbi.nlm.nih.gov/pubmed/32108443
http://dx.doi.org/10.1002/cam4.2945
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