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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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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. |
format | Online Article Text |
id | pubmed-7196059 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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