In the phase II AC220-002 trial, investigators enrolled 271 patients with primary AML or AML secondary to the myelodysplastic syndrome.
One cohort enrolled 133 patients aged 60 years and older who had had their first relapse within the previous year or were refractory to first-line therapy. In this cohort, 90 patients were FLT3-ITD positive.
The other cohort included 138 patients 18 and older (100 FLT3-ITD–positive) who had relapsed after or were refractory to second-line treatment or HSCT.
In the older-patient cohort described by Dr. Cortes, the CRc rate (a composite of complete remissions plus complete remissions with incomplete platelet and/or hematologic recovery) in FLT3-ITD–positive patients was 50%, and the partial response rate was 21%. Among FLT3-ITD–negative patients, the CRc rate was 36%, and the PR rate was 10%.
In these patients, 70% of those carrying the mutation and 55% of those without the mutation who had been refractory to their last prior therapy achieved at least a partial response. The median duration of remission was 10.4 weeks for FLT3-ITD–positive patients, and 9.3 weeks for –negative patients.
Patients tolerated the drug very well, with the most serious event being a reversible prolongation of the QT interval, and dose-limiting myelosuppression, possibly related to inhibition of the KIT kinase, said Dr. Levis.
The study was funded by Ambit Biosciences, maker of quizartinib (AC220). Dr. Levis disclosed serving as a consultant to the company. Dr. Cortes disclosed serving as a consultant to Novartis.