PMID- 32108443
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 9
IP  - 9
DP  - 2020 May
TI  - 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.
PG  - 2989-2996
LID - 10.1002/cam4.2945 [doi]
AB  - 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.
CI  - (c) 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Moreau, Philippe
AU  - Moreau P
AUID- ORCID: 0000-0003-1780-8746
AD  - University Hospital of Nantes, Nantes, France.
FAU - Stewart, Keith A
AU  - Stewart KA
AD  - Mayo Clinic, Scottsdale, AZ, USA.
FAU - Dimopoulos, Meletios
AU  - Dimopoulos M
AD  - School of Medicine, National and Kapodistrian University of Athens, Athens, 
      Greece.
FAU - Siegel, David
AU  - Siegel D
AD  - John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, 
      USA.
FAU - Facon, Thierry
AU  - Facon T
AD  - Hopital Claude Huriez, Lille University Hospital, Lille, France.
FAU - Berenson, James
AU  - Berenson J
AD  - Institute for Myeloma & Bone Cancer Research, West Hollywood, CA, USA.
FAU - Raje, Noopur
AU  - Raje N
AD  - Massachusetts General Hospital Cancer Center, Boston, MA, USA.
FAU - Berdeja, Jesus G
AU  - Berdeja JG
AD  - Sarah Cannon Research Institute, Nashville, TN, USA.
FAU - Orlowski, Robert Z
AU  - Orlowski RZ
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Yang, Hui
AU  - Yang H
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Ma, Haijun
AU  - Ma H
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Klippel, Zandra
AU  - Klippel Z
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Zahlten-Kumeli, Anita
AU  - Zahlten-Kumeli A
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Mezzi, Khalid
AU  - Mezzi K
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Iskander, Karim
AU  - Iskander K
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Mateos, Maria-Victoria
AU  - Mateos MV
AD  - University Hospital Salamanca/IBSAL, Salamanca, Spain.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200228
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Oligopeptides)
RN  - 72X6E3J5AR (carfilzomib)
SB  - IM
MH  - Aged
MH  - Clinical Trials, Phase III as Topic
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multicenter Studies as Topic
MH  - Multiple Myeloma/*drug therapy/pathology
MH  - Neoplasm Recurrence, Local/*drug therapy/pathology
MH  - Oligopeptides/*therapeutic use
MH  - Prognosis
MH  - Randomized Controlled Trials as Topic
MH  - Salvage Therapy
MH  - Survival Rate
PMC - PMC7196059
OTO - NOTNLM
OT  - carfilzomib
OT  - dosing schedule
OT  - once-weekly
OT  - relapsed and/or refractory multiple myeloma
EDAT- 2020/02/29 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/02/28
CRDT- 2020/02/29 06:00
PHST- 2019/08/15 00:00 [received]
PHST- 2020/01/17 00:00 [revised]
PHST- 2020/02/12 00:00 [accepted]
PHST- 2020/02/29 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/02/29 06:00 [entrez]
PHST- 2020/02/28 00:00 [pmc-release]
AID - CAM42945 [pii]
AID - 10.1002/cam4.2945 [doi]
PST - ppublish
SO  - Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.