TY - JOUR
T1 - Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma
T2 - Updated Overall Survival, Safety, and Subgroups
AU - Orlowski, Robert Z.
AU - Moreau, Philippe
AU - Niesvizky, R.
AU - Ludwig, H.
AU - Oriol, Albert
AU - Chng, Wee Joo
AU - Goldschmidt, Hartmut
AU - Yang, Zhao
AU - Kimball, A. S.
AU - Dimopoulos, Meletios
N1 - Funding Information:
Onyx Pharmaceuticals, Inc , an Amgen subsidiary, funded the ENDEAVOR study and was involved in study design; collection, analysis, and interpretation of data; in the writing of this report; and in the decision to submit this article for publication. Medical writing assistance was provided by BlueMomentum, an Ashfield company, part of UDG Healthcare PLC, and Guerry Cook and Yin C. Lin of Amgen, Inc, and funded by Amgen .
Funding Information:
R.Z.O. reports consultancy or advisory board participation for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Kite Pharma, Sanofi-Aventis, and Takeda, and grant or research support from Amgen, BioTheryX, and Spectrum Pharma. P.M. reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis, Onyx, and Takeda, and consulting or advisory role fees from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis, Onyx, and Takeda. R.N. reports consultancy for Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. H.L. reports serving in a consulting or advisory role for Amgen, Cilag-Janssen, and Takeda, serving on the speakers? bureau for Amgen, Bristol-Myers Squibb, Celgene, Cilag-Janssen, and Takeda, and receiving research funding from Amgen and Takeda. A.O. reports serving in a consulting or advisory role for Amgen, Celgene, Janssen, and Takeda, and serving on the speakers? bureaus for Amgen and Janssen. W.J.C. reports honoraria from Amgen, Celgene, Janssen, Novartis, Roche, and Takeda, and research funding from Celgene, Janssen, Merck, Novartis, and Roche. H.G. reports research support from Amgen, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Mundipharma, Novartis, Sanofi, and Takeda, advisory board participant for Adaptive Biotechnology, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Sanofi-Aventis, and Takeda, and honoraria for participant in speakers? bureaus for ArtTempi, Bristol-Myers Squibb, Celgene, Chugai, Janssen, and Novartis. Z.Y. reports employment with and stock holdings from Amgen. A.S.K. reports employment with Amgen and stock holdings from Amgen and WindMIL. M.D. reports consulting or advisory role fees from Amgen, Celgene, Janssen, Novartis, and Takeda, research funding from Genesis Pharma, and honoraria from Amgen, Celgene, Janssen, Novartis, and Takeda.Onyx Pharmaceuticals, Inc, an Amgen subsidiary, funded the ENDEAVOR study and was involved in study design; collection, analysis, and interpretation of data; in the writing of this report; and in the decision to submit this article for publication. Medical writing assistance was provided by BlueMomentum, an Ashfield company, part of UDG Healthcare PLC, and Guerry Cook and Yin C. Lin of Amgen, Inc, and funded by Amgen.
Funding Information:
R.Z.O. reports consultancy or advisory board participation for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Kite Pharma, Sanofi-Aventis, and Takeda, and grant or research support from Amgen, BioTheryX, and Spectrum Pharma. P.M. reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis, Onyx, and Takeda, and consulting or advisory role fees from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis, Onyx, and Takeda. R.N. reports consultancy for Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. H.L. reports serving in a consulting or advisory role for Amgen, Cilag-Janssen, and Takeda, serving on the speakers’ bureau for Amgen, Bristol-Myers Squibb, Celgene, Cilag-Janssen, and Takeda, and receiving research funding from Amgen and Takeda. A.O. reports serving in a consulting or advisory role for Amgen, Celgene, Janssen, and Takeda, and serving on the speakers’ bureaus for Amgen and Janssen. W.J.C. reports honoraria from Amgen, Celgene, Janssen, Novartis, Roche, and Takeda, and research funding from Celgene, Janssen, Merck, Novartis, and Roche. H.G. reports research support from Amgen, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Mundipharma, Novartis, Sanofi, and Takeda, advisory board participant for Adaptive Biotechnology, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Sanofi-Aventis, and Takeda, and honoraria for participant in speakers’ bureaus for ArtTempi, Bristol-Myers Squibb, Celgene, Chugai, Janssen, and Novartis. Z.Y. reports employment with and stock holdings from Amgen. A.S.K. reports employment with Amgen and stock holdings from Amgen and WindMIL. M.D. reports consulting or advisory role fees from Amgen, Celgene, Janssen, Novartis, and Takeda, research funding from Genesis Pharma, and honoraria from Amgen, Celgene, Janssen, Novartis, and Takeda.Onyx Pharmaceuticals, Inc, an Amgen subsidiary, funded the ENDEAVOR study and was involved in study design; collection, analysis, and interpretation of data; in the writing of this report; and in the decision to submit this article for publication. Medical writing assistance was provided by BlueMomentum, an Ashfield company, part of UDG Healthcare PLC, and Guerry Cook and Yin C. Lin of Amgen, Inc, and funded by Amgen.
Publisher Copyright:
© 2019 The Authors
PY - 2019/8
Y1 - 2019/8
N2 - Introduction: The phase III RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial showed significantly improved progression-free survival and overall survival (OS) with carfilzomib (56 mg/m2) and dexamethasone (Kd56) versus bortezomib and Kd56 (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). We report updated OS and safety data after 6 months of additional follow-up. Patients and Methods: Patients with RRMM (1-3 previous lines of therapy) were randomized 1:1 to Kd56 or Vd. Median OS was estimated using the Kaplan–Meier method; OS was compared between treatment groups using Cox proportional hazards models. Results: As of July 19, 2017, median follow-up was 44.3 months for Kd56 and 43.7 months for Vd. Median OS was 47.8 months (Kd56) versus 38.8 months (Vd; hazard ratio, 0.76; 95% confidence interval, 0.633-0.915). OS was longer with Kd56 versus Vd within age and cytogenetic subgroups, and according to number of previous lines of therapy, previous bortezomib exposure, previous lenalidomide exposure, and lenalidomide-refractory status. Exposure-adjusted incidences per 100 patient-years of adverse events (AEs) were 1352.07 for Kd56 and 1754.86 for Vd; for Grade ≥3 AEs, these values were 162.31 and 175.90. Conclusion: With median follow-up of approximately 44 months, clinically meaningful improvements in OS were observed with Kd56 versus Vd, including in all subgroups examined. The Kd56 safety profile was consistent with previous analyses. In this updated analysis of patients with relapsed/refractory multiple myeloma (RRMM) from the RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial, clinically meaningful overall survival improvements continue to be observed with carfilzomib 56 mg/m2 and dexamethasone (Kd56; n = 464) versus bortezomib and dexamethasone (n = 465), including in key patient subgroups. With longer-term data, the favorable benefit-risk profile of Kd56 continues to support its use as a standard-of-care in RRMM.
AB - Introduction: The phase III RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial showed significantly improved progression-free survival and overall survival (OS) with carfilzomib (56 mg/m2) and dexamethasone (Kd56) versus bortezomib and Kd56 (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). We report updated OS and safety data after 6 months of additional follow-up. Patients and Methods: Patients with RRMM (1-3 previous lines of therapy) were randomized 1:1 to Kd56 or Vd. Median OS was estimated using the Kaplan–Meier method; OS was compared between treatment groups using Cox proportional hazards models. Results: As of July 19, 2017, median follow-up was 44.3 months for Kd56 and 43.7 months for Vd. Median OS was 47.8 months (Kd56) versus 38.8 months (Vd; hazard ratio, 0.76; 95% confidence interval, 0.633-0.915). OS was longer with Kd56 versus Vd within age and cytogenetic subgroups, and according to number of previous lines of therapy, previous bortezomib exposure, previous lenalidomide exposure, and lenalidomide-refractory status. Exposure-adjusted incidences per 100 patient-years of adverse events (AEs) were 1352.07 for Kd56 and 1754.86 for Vd; for Grade ≥3 AEs, these values were 162.31 and 175.90. Conclusion: With median follow-up of approximately 44 months, clinically meaningful improvements in OS were observed with Kd56 versus Vd, including in all subgroups examined. The Kd56 safety profile was consistent with previous analyses. In this updated analysis of patients with relapsed/refractory multiple myeloma (RRMM) from the RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial, clinically meaningful overall survival improvements continue to be observed with carfilzomib 56 mg/m2 and dexamethasone (Kd56; n = 464) versus bortezomib and dexamethasone (n = 465), including in key patient subgroups. With longer-term data, the favorable benefit-risk profile of Kd56 continues to support its use as a standard-of-care in RRMM.
KW - Clinical outcomes
KW - Efficacy
KW - Phase III
KW - Proteasome inhibitor
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U2 - 10.1016/j.clml.2019.04.018
DO - 10.1016/j.clml.2019.04.018
M3 - Article
C2 - 31160237
AN - SCOPUS:85066323327
SN - 2152-2650
VL - 19
SP - 522-530.e1
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 8
ER -