FDA Approves Quizartinib for Newly Diagnosed FLT3-ITD+ AML

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Data from the phase 3 QuANTUM-First trial support the FDA’s approval of quizartinib for managing FLT3-ITD–positive acute myeloid leukemia.

"One of the things that [the QuANTUM-First] trial does is it shows, very clearly in a population of patients that included older adults, that [quizartinib] was effective," according to Mikkael A. Sekeres, MD.

"One of the things that [the QuANTUM-First] trial does is it shows, very clearly in a population of patients that included older adults, that [quizartinib] was effective," according to Mikkael A. Sekeres, MD.

The FDA approved quizartinib (Vanflyta) in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy for the treatment of patients with newly diagnosed FLT3-ITD–positive acute myeloid leukemia (AML), according to a press release from the FDA.1

The quizartinib regimen was assessed as part of the the phase 3 QuANTUM-First trial (NCT02668653)2. The quizartinib combination resulted in a statistically significant OS benefit vs the comparator arm (HR, 0.78; 95% CI, 0.62-0.98; 2-sided P = .0324).

In a presentation at the 2022 European Hematology Association Congress, quizartinib yielded a median overall survival (OS) of 31.9 months (95% CI, 21.0-not estimable [NE]) vs 15.1 months (95% CI, 13.2-26.2) with placebo (HR, 0.776; 95% CI, 0.615-0.979; P = .0324).

“I do think this [approval] represents a step forward for patients who have the FLT3 mutation in association with their [AML] over the previous standard, midostaurin [Rydapt],” study author Mikkael A. Sekeres, MD, said in an interview with CancerNetwork® ahead of the approval.

Sekeres, chief of the Division of Hematology at Sylvester Comprehensive Cancer Center of the University of Miami Health System and Communications Committee Chair for the American Society of Hematology (ASH), spoke about how quizartinib’s approval would offer older patients with AML a potentially more suitable treatment option compared with midostaurin.

“The [phase 3] RATIFY trial [NCT00651261], which led to midostaruin's [FDA] approval [in AML], included patients up to age 59. It really didn't include older adults,” Sekeres said. “one of the things that [the QuANTUM-First] trial does is it shows, very clearly in a population of patients that included older adults, that [quizartinib] was effective.”

The FDA approved midostaurin for newly diagnosed FLT3-mutated AML in April 2017.3

The QuANTUM-First trial included patients aged 18 to 75 years with newly diagnosed primary or secondary AML harboring a FLT3-ITD activating mutation with an allelic ratio of 3% or more. Patients were randomly assigned 1:1 to receive chemotherapy plus quizartinib (n = 268) or placebo (n = 271). Induction involved up to 2 cycles of cytarabine plus daunorubicin/idaribicin followed by quizartinib or placebo, consolidation for up 4 cycles with cytarabine followed by quizartinib or placebo and/or hematopoietic stem cell transplant, and up to 36 cycles of quizartinib or placebo.

The primary end point of the trial was OS. Secondary end points included event-free survival (EFS), complete remission (CR) rate, CR composite (CRc) rate, safety, and pharmacokinetics.

Investigators reported that neither quizartinib or placebo yielded a statistically significant benefit in terms of EFS (HR, 0.916; 95% CI, 0.754-1.114; P = .2371). This trend occurred even while controlling for patients who did not achieve a CR by day 42 of the last cycle of induction (HR, 0.818; 95% CI, 0.669-0.999; P = .0323).

In the quizartinib and placebo arms, respectively, the CR rate was 54.9% (95% CI, 48.7%-60.9%) vs 55.4% (95% CI, 49.2%-61.4%), and the CRc rate was 71.6% (95% CI, 65.8%-77.0%) vs 64.9% (95% CI, 58.9%-70.6%). Additionally, duration of CR was 38.6 months (95% CI, 21.9-NE) vs 12.4 months (95% CI, 8.8-22.7), respectively, and RFS for those who achieved CR was 39.3 months vs 13.6 months (HR, 0.613; 95% CI, 0.444-0.845).

Frequent grade 3 treatment-emergent adverse effects in the quizartinib and placebo arms, respectively, included febrile neutropenia (43.4% vs 41.0%), hypokalemia (18.9% vs 16.4%), and pneumonia (11.7% vs 12.7%). Additionally, 2.3% of patients receiving quizartinib experienced QTcF prolongation and 0.8% discontinued treatment as a result. Additionally, 2 patients with severe hypokalemia suffered cardiac arrest, and 1 patient died as a result.

The FDA granted priority review to quizartinib for newly diagnosed FLT3-ITD–positive AML in October 2022.4

References

  1. FDA approves quizartinib for newly diagnosed acute myeloid leukemia. News release. FDA. July 20, 2023. Accessed July 20, 2023. https://bit.ly/3K6SH6K
  2. Erba H, Montesinos P, Vrhovac R, et al. Quizartinib prolongs survival vs placebo plus intensive induction and consolidation therapy followed by single-agent continuation in patients aged 18-75 years with newly diagnosed FLT3-ITD+ AML. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S100.
  3. Midostaurin. News release. FDA. April 28, 2017. Accessed July 18, 2023. https://rb.gy/5pvas
  4. Quizartinib granted priority review in the U.S for patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia. News release. Daiichi Sankyo. October 24, 2022. Accessed October 24, 2022. https://bit.ly/3N2RPQs
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