TY - JOUR
T1 - Guadecitabine vs treatment choice in newly diagnosed acute myeloid leukemia
T2 - A global phase 3 randomized study
AU - Fenaux, Pierre
AU - Gobbi, Marco
AU - Kropf, Patricia L.
AU - Issa, Jean Pierre J.
AU - Roboz, Gail J.
AU - Mayer, Jiri
AU - Krauter, Jörgen
AU - Robak, Tadeusz
AU - Kantarjian, Hagop
AU - Novak, Jan
AU - Jedrzejczak, Wieslaw W.
AU - Thomas, Xavier
AU - Ojeda-Uribe, Mario
AU - Miyazaki, Yasushi
AU - Min, Yoohong
AU - Yeh, Su Peng
AU - Brandwein, Joseph
AU - Gercheva-Kyuchukova, Liana
AU - Demeter, Judit
AU - Griffiths, Elizabeth
AU - Yee, Karen
AU - Döhner, Konstanze
AU - Hao, Yong
AU - Keer, Harold
AU - Azab, Mohammad
AU - Döhner, Hartmut
N1 - Publisher Copyright:
© 2023 American Society of Hematology. All rights reserved.
PY - 2023/9/12
Y1 - 2023/9/12
N2 - 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.
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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85168362178&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2023010179
DO - 10.1182/bloodadvances.2023010179
M3 - Article
C2 - 37276510
AN - SCOPUS:85168362178
SN - 2473-9529
VL - 7
SP - 5027
EP - 5037
JO - Blood Advances
JF - Blood Advances
IS - 17
ER -