PMID- 37276510
OWN - NLM
STAT- MEDLINE
DCOM- 20230829
LR  - 20230906
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 7
IP  - 17
DP  - 2023 Sep 12
TI  - Guadecitabine vs treatment choice in newly diagnosed acute myeloid leukemia: a 
      global phase 3 randomized study.
PG  - 5027-5037
LID - 10.1182/bloodadvances.2023010179 [doi]
AB  - This phase 3 study evaluated the efficacy and safety of the new hypomethylating 
      agent guadecitabine (n = 408) vs a preselected treatment choice (TC; n = 407) of 
      azacitidine, decitabine, or low-dose cytarabine in patients with acute myeloid 
      leukemia unfit to receive intensive induction chemotherapy. Half of the patients 
      (50%) had poor Eastern Cooperative Oncology Group Performance Status (2-3). The 
      coprimary end points were complete remission (19% and 17% of patients for 
      guadecitabine and TC, respectively [stratified P = .48]) and overall survival 
      (median survival 7.1 and 8.5 months for guadecitabine and TC, respectively 
      [hazard ratio, 0.97; 95% confidence interval, 0.83-1.14; stratified log-rank 
      P = .73]). One- and 2-year survival estimates were 37% and 18% for guadecitabine 
      and 36% and 14% for TC, respectively. A large proportion of patients (42%) 
      received <4 cycles of treatment in both the arms. In a post hoc analysis of 
      patients who received >/=4 treatment cycles, guadecitabine was associated with 
      longer median survival vs TC (15.6 vs 13.0 months [hazard ratio, 0.78; 95% 
      confidence interval, 0.64-0.96; log-rank P = .02]). There was no significant 
      difference in the proportion of patients with grade >/=3 adverse events (AEs) 
      between guadecitabine (92%) and TC (88%); however, grade >/=3 AEs of febrile 
      neutropenia, neutropenia, and pneumonia were higher with guadecitabine. In 
      conclusion, no significant difference was observed in the efficacy of 
      guadecitabine and TC in the overall population. This trial was registered at 
      www.clinicaltrials.gov as #NCT02348489.
CI  - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Fenaux, Pierre
AU  - Fenaux P
AD  - Hopital Saint-Louis, Paris, France.
FAU - Gobbi, Marco
AU  - Gobbi M
AD  - Ospedale Policlinico San Martino, Genova, Italy.
FAU - Kropf, Patricia L
AU  - Kropf PL
AD  - Novant Health Cancer Institute - Elizabeth, Charlotte, NC.
FAU - Issa, Jean-Pierre J
AU  - Issa JJ
AD  - Coriell Institute for Medical Research, Camden, NJ.
FAU - Roboz, Gail J
AU  - Roboz GJ
AUID- ORCID: 0000-0002-0384-3658
AD  - Weill Cornell Medicine, New York, NY.
FAU - Mayer, Jiri
AU  - Mayer J
AD  - Fakultni Nemocnice, Brno, Ceska Republika.
FAU - Krauter, Jurgen
AU  - Krauter J
AD  - Stadtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany.
FAU - Robak, Tadeusz
AU  - Robak T
AUID- ORCID: 0000-0002-3411-6357
AD  - Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland.
FAU - Kantarjian, Hagop
AU  - Kantarjian H
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX.
FAU - Novak, Jan
AU  - Novak J
AD  - Univerzita Karlova, Praha, Ceska Republika.
FAU - Jedrzejczak, Wieslaw W
AU  - Jedrzejczak WW
AUID- ORCID: 0000-0002-6813-3331
AD  - Samodzielny Publiczny Centralny Szpital Kliniczny, Warszawa, Poland.
FAU - Thomas, Xavier
AU  - Thomas X
AD  - Hopital Lyon Sud, Pierre Benite, France.
FAU - Ojeda-Uribe, Mario
AU  - Ojeda-Uribe M
AD  - GHR Mulhouse Sud-Alsace, Mulhouse, France.
FAU - Miyazaki, Yasushi
AU  - Miyazaki Y
AD  - Nagasaki University Hospital, Nagasaki, Japan.
FAU - Min, Yoo Hong
AU  - Min YH
AD  - Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
FAU - Yeh, Su-Peng
AU  - Yeh SP
AD  - China Medical University Hospital, Taichung City, Taiwan.
FAU - Brandwein, Joseph
AU  - Brandwein J
AUID- ORCID: 0000-0001-9095-8789
AD  - University of Alberta Hospital, Edmonton, Canada.
FAU - Gercheva-Kyuchukova, Liana
AU  - Gercheva-Kyuchukova L
AD  - Hospital "St. Marina" EAD, Varna, Bulgaria.
FAU - Demeter, Judit
AU  - Demeter J
AUID- ORCID: 0000-0001-8745-0757
AD  - Semmelweis Egyetem, Budapest, Hungary.
FAU - Griffiths, Elizabeth
AU  - Griffiths E
AUID- ORCID: 0000-0002-0288-8248
AD  - Roswell Park Comprehensive Cancer Institute, Buffalo, NY.
FAU - Yee, Karen
AU  - Yee K
AUID- ORCID: 0000-0002-2572-9952
AD  - Princess Margaret Cancer Centre, Toronto, ON, Canada.
FAU - Dohner, Konstanze
AU  - Dohner K
AD  - Ulm University Hospital, Ulm, Germany.
FAU - Hao, Yong
AU  - Hao Y
AD  - Astex Pharmaceuticals Inc, Pleasanton, CA.
FAU - Keer, Harold
AU  - Keer H
AD  - Astex Pharmaceuticals Inc, Pleasanton, CA.
FAU - Azab, Mohammad
AU  - Azab M
AD  - Astex Pharmaceuticals Inc, Pleasanton, CA.
FAU - Dohner, Hartmut
AU  - Dohner H
AUID- ORCID: 0000-0003-2116-5536
AD  - Ulm University Hospital, Ulm, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT02348489
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 2KT4YN1DP7 (guadecitabine)
RN  - M801H13NRU (Azacitidine)
RN  - 04079A1RDZ (Cytarabine)
SB  - IM
MH  - Humans
MH  - Treatment Outcome
MH  - *Azacitidine/adverse effects
MH  - Cytarabine/adverse effects
MH  - *Leukemia, Myeloid, Acute/diagnosis/drug therapy
PMC - PMC10471926
COIS- Conflict-of-interest disclosure: P.F. has received honoraria and (as Groupe 
      Francophone des Myelodysplasies chairperson) research funds from Astex, AbbVie, 
      Bristol Myers Squibb, Novartis, and Janssen; P.L.K. has received consulting fees 
      from BMS and Takeda; J.-P.J.I. has received clinical research support from Astex, 
      and consulting fees from Ascentage and Daiichi; G.J.R. has consulted for Astex, 
      AbbVie, Actinium, Agios, Amgen, Astellas, Bayer, Bristol Myers Squibb, Celltrion, 
      Celgene, Daiichi, Genentech/Roche, GSK, Helsinn, Janssen, Jasper, Jazz, 
      MedImmune, Mesoblast, Novartis, Otsuka, MEI, Pfizer, Sandoz, and Takeda, and has 
      received research funding from Astex, AbbVie, Agios, Amphivena, Celgene, CTI, 
      Janssen, Karyopharm, MedImmune, MEI, Moffitt Cancer Center, Novartis, Onconova, 
      Sunesis, and Tensha, honoraria from Pfizer, and travel expenses from Astex, 
      AbbVie, Agios, Amgen, Amphivena, Array, Bayer, Celgene, Celltrion, Clovis, Eisai, 
      Genentech/Roche, Janssen, Jazz, Novartis, Pfizer, Sandoz, and Sunesis; J.M. has 
      participated on an advisory board and received honoraria from Astex; T.R. has 
      received grants from and participated on an advisory board for Astex; H. 
      Kantarjian has received grants from AbbVie, Amgen, Ascentage, Bristol Myers 
      Squibb, Daiichi-Sankyo, ImmunoGen, Jazz, and Novartis, and honoraria from AbbVie, 
      Amgen, Amphista, Ascentage, Astellas, Biologix, Curis, Ipsen, KAHRl, Labcorp, 
      Novartis, Pfizer, Shenzhen Target Rx, Stemline, and Takeda; J.N. has consulted 
      for AbbVie, Amgen, Astellas, Novartis, Pfizer, Roche, and Takeda, and received 
      travel expenses from Amgen and Janssen; Y.M. has received honoraria from AbbVie, 
      Amgen, Astellas, BMS, Chugai, Janssen, Kyowa-Kirin, Nippon-Shinyaku, Novartis, 
      Otsuka, Pfizer, Sumitomo, and Takeda, and clinical research funding (to 
      institution) from Chugai; S.-P.Y. has participated on advisory boards for Astex, 
      AbbVie, Amgen, Astellas, and Janssen; J.B. has received honoraria from AbbVie, 
      Amgen, Astellas, Avir, BMS/Celgene, Jazz, Paladin, Pfizer, and Taiho; J.D. has 
      participated in advisory committees for Amgen, Amicus, Angelini, Bristol Myers 
      Squibb, Novartis, Pfizer, and Roche; E.G. has received research funding (to 
      Roswell Park) from Alexion, Astex, Blueprint, Celgene, Celldex, and Genentech, 
      consulting fees from AbbVie, Alexion, Apellis, AstraZeneca, Celgene, CTI, 
      Genentech, Novartis, Taiho, and Takeda, honoraria from AAMDSIF, American Society 
      of Hematology, Highlights of American Society of Hematology, MediCom, Physicians 
      Educational Resource, and Picnic Health, and laboratory material from Imago, and 
      participated in an advisory board for Dresner Foundation; K.Y. has received 
      research funding from Astex, Forma, Geron, Gilead, Janssen, Jazz, Karyopharm, 
      Novartis, Onconova, Roche, and Treadwell, and honoraria from AbbVie, Amgen, and 
      Novartis, and participated in advisory boards for Astellas, BMS/Celgene, GSK, 
      Jazz, Novartis, Pfizer, Roche, Shattuck, Taiho, and Takeda; K.D. has received 
      research funding from Agios, Astellas, Celgene/BMS, and Novartis, and honoraria 
      from Celgene/BMS, Daiichi Sankyo, Jazz, Novartis, and Roche, and participated in 
      advisory boards for AbbVie, Celgene/BMS, Daiichi Sankyo, Jazz, Novartis, and 
      Roche; Y.H., H.K., and M.A. are employees of Astex; H.D. has received honoraria 
      from AbbVie, Agios, Amgen, Astellas, AstraZeneca, Berlin-Chemie, Bristol Myers 
      Squibb, Celgene, GEMoaB, Gilead, Janssen, Jazz, Novartis, Servier, and Syndax, 
      and clinical research funding (to institution) from AbbVie, Agios, Amgen, 
      Astellas, Bristol Myers Squibb, Celgene, Jazz, Kronos, and Novartis. The 
      remaining authors declare no competing financial interests.
EDAT- 2023/06/05 19:10
MHDA- 2023/08/29 12:43
PMCR- 2023/06/07
CRDT- 2023/06/05 16:13
PHST- 2023/05/21 00:00 [accepted]
PHST- 2023/03/13 00:00 [received]
PHST- 2023/08/29 12:43 [medline]
PHST- 2023/06/05 19:10 [pubmed]
PHST- 2023/06/05 16:13 [entrez]
PHST- 2023/06/07 00:00 [pmc-release]
AID - 496179 [pii]
AID - 10.1182/bloodadvances.2023010179 [doi]
PST - ppublish
SO  - Blood Adv. 2023 Sep 12;7(17):5027-5037. doi: 10.1182/bloodadvances.2023010179.