TY - JOUR
T1 - Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD–mutated, relapsed or refractory AML
AU - Cortes, Jorge E.
AU - Tallman, Martin S.
AU - Schiller, Gary J.
AU - Trone, Denise
AU - Gammon, Guy
AU - Goldberg, Stuart L.
AU - Perl, Alexander E.
AU - Marie, Jean Pierre
AU - Martinelli, Giovanni
AU - Kantarjian, Hagop M.
AU - Levis, Mark J.
N1 - Funding Information:
Financial support for medical editorial assistance was provided by Daiichi Sankyo. This work was supported in part by the National Institutes of Health, National Cancer Institute Leukemia SPORE P50 CA100632 (J.E.C., H.M.K., and M.J.L.) and Cancer Center Support grant P30 CA16672 (J.E.C. and H.M.K.). This study was sponsored by Daiichi Sankyo, Inc., a member of the Daiichi Sankyo Group.
Funding Information:
The authors thank Vinay Pasupuleti, Accuverus Inc., for his medical editorial assistance with this manuscript. Financial support for medical editorial assistance was provided by Daiichi Sankyo. This work was supported in part by the National Institutes of Health, National Cancer Institute Leukemia SPORE P50 CA100632 (J.E.C., H.M.K., and M.J.L.) and Cancer Center Support grant P30 CA16672 (J.E.C. and H.M.K.). This study was sponsored by Daiichi Sankyo, Inc., a member of the Daiichi Sankyo Group.
Publisher Copyright:
Copyright 2011 by The American Society of Hematology; all rights reserved.
PY - 2018/8/9
Y1 - 2018/8/9
N2 - This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/ refractory (R/R) FLT3-internal tandem duplication (ITD)–mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N 5 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD–mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia’s formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day.
AB - This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/ refractory (R/R) FLT3-internal tandem duplication (ITD)–mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N 5 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD–mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia’s formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day.
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U2 - 10.1182/blood-2018-01-821629
DO - 10.1182/blood-2018-01-821629
M3 - Article
C2 - 29875101
AN - SCOPUS:85051362179
SN - 0006-4971
VL - 132
SP - 598
EP - 607
JO - Blood
JF - Blood
IS - 6
ER -