Dr Fedorov on the Use of Quizartinib vs Midostaurin in FLT3+ AML

Kateryna Fedorov, MD, assistant professor, hematology-oncology, Vanderbilt University Medical Center, discusses disease factors and patient characteristics to consider when deciding between treatment with quizartinib (Vanflyta) and midostaurin (Rydapt) for patients with 

FDA approval of quizartinib plus chemotherapy

-ITD–positive AML, the AML field has needed to reassess optimal treatment strategies with this agent vs midostaurin for patients with both 

-TKD–mutated AML, Fedorov says. Prior to the approval of quizartinib, all patients with 

-mutated AML who were receiving induction 7 + 3 chemotherapy received midostaurin, Fedorov explains. Although midostaurin is an effective agent that induces durable complete responses, many patients cannot tolerate this therapy because of associated gastrointestinal adverse effects and muscle aches, Fedorov notes.

Conversely, quizartinib is a more precise, selective FLT3 inhibitor that only targets 

-ITD mutations, Fedorov emphasizes. However, questions remain regarding when this agent should be considered for patients with 

-ITD–mutated AML, according to Fedorov. The pivotal phase 3 QuANTUM-First trial (NCT02668653) demonstrated remission rates with quizartinib that were comparable with those seen in the phase 3 RATIFY trial (NCT00651261), which led to the 2017 

 combined with standard 7 + 3 chemotherapy for patients with newly diagnosed 

-positive AML. However, QuANTUM-First also showed a lower median overall survival with quizartinib than RATIFY did with midostaurin.

Although quizartinib appears to better tolerated than midostaurin, it is associated with QT prolongation, which needs to be monitored, Fedorov says. Additionally, one goal of QuANTUM-First was to determine whether older patients with AML would benefit from quizartinib. However, findings showed that younger patients benefit most from treatment with this agent, Fedorov explains. Moreover, gaining timely access to quizartinib for each patient may prove challenging, as patients’ 

 ITD mutation status must be identified before they are deemed eligible to receive this treatment, according to Fedorov. The logistics of incorporating quizartinib into real-world clinical practice may need to be refined going forward, Fedorov concludes. 

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Kateryna Fedorov, MD, discusses considerations when deciding between quizartinib and midostaurin for patients with FLT3-mutated AML.

Kateryna Fedorov, MD

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Dr Fedorov on the Use of Quizartinib vs Midostaurin in FLT3+ AML