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Clinical Trial
. 2023 Sep 12;7(17):5027-5037.
doi: 10.1182/bloodadvances.2023010179.

Guadecitabine vs treatment choice in newly diagnosed acute myeloid leukemia: a global phase 3 randomized study

Pierre Fenaux  1 , Marco Gobbi  2 , Patricia L Kropf  3 , Jean-Pierre J Issa  4 , Gail J Roboz  5 , Jiri Mayer  6 , Jürgen Krauter  7 , Tadeusz Robak  8 , Hagop Kantarjian  9 , Jan Novak  10 , Wieslaw W Jedrzejczak  11 , Xavier Thomas  12 , Mario Ojeda-Uribe  13 , Yasushi Miyazaki  14 , Yoo Hong Min  15 , Su-Peng Yeh  16 , Joseph Brandwein  17 , Liana Gercheva-Kyuchukova  18 , Judit Demeter  19 , Elizabeth Griffiths  20 , Karen Yee  21 , Konstanze Döhner  22 , Yong Hao  23 , Harold Keer  23 , Mohammad Azab  23 , Hartmut Döhner  22
Affiliations
Clinical Trial

Guadecitabine vs treatment choice in newly diagnosed acute myeloid leukemia: a global phase 3 randomized study

Pierre Fenaux et al. Blood Adv. .

Abstract

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.

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Conflict of interest statement

Conflict-of-interest disclosure: P.F. has received honoraria and (as Groupe Francophone des Myélodysplasies 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.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patient Assignments and Disposition. Pre- and postrandomization assignments (A) and overall patient disposition (B). DEC, decitabine; G, guadecitabine AZA, azacitidine, LDAC, low dose Ara-C.
Figure 2.
Figure 2.
Survival analysis (efficacy analysis set). Coprimary end point of OS.
Figure 3.
Figure 3.
Survival analysis of patients with ≥4 cycles (n = 476).
Figure 4.
Figure 4.
Forest plot of OS in prospective subgroups (A) and in patients who received ≥4 cycles of treatment (B). LCL, lower confidence limit; ROW, rest of world; UCL, upper confidence limit.
See this image and copyright information in PMC

References

    1. Sasaki K, Ravandi F, Kadia TM, et al. De novo acute myeloid leukemia: a population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer. 2021;127(12):2049–2061. - PMC - PubMed
    1. Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed acute myeloid leukemia with >30% blasts. Blood. 2015;126(3):291–299. - PMC - PubMed
    1. Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670–2677. - PMC - PubMed
    1. DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7–17. - PMC - PubMed
    1. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–629. - PubMed

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