Quizartinib/Chemo Shows Superior OS Benefit Over Chemo Alone in Newly Diagnosed FLT3-ITD+ AML

The addition of quizartinib to chemotherapy resulted in a statistically significant and clinically meaningful improvement in overall survival vs standard chemotherapy alone in patients with newly diagnosed, FLT3-ITD–positive acute myeloid leukemia.

The addition of quizartinib to standard induction and consolidation chemotherapy followed by quizartinib monotherapy resulted in a statistically significant and clinically meaningful improvement in overall survival (OS) vs standard chemotherapy alone in patients with newly diagnosed, FLT3-ITD–positive acute myeloid leukemia (AML), meeting the primary end point of the phase 3 QuANTUM-First trial (NCT02668653).1

Moreover, the oral, highly potent and selective type II FLT3 inhibitor was found to have a manageable safety profile with no new signals observed.

Daiichi Sankyo Company Limited, the drug developer, shared that findings from the trial will be presented at an upcoming medical conference. The data will also be shared with global regulatory authorities.

“The results of the phase QuANTUM-First trial showed that adding quizartinib, a potent and selective FLT3 inhibitor, to chemotherapy significantly prolonged OS in patients with newly diagnosed FLT3-ITD–positive AML,” Ken Takeshita, MD, global head of Research & Development at Daiichi Sankyo, stated in a press release. “We look forward to sharing the QuANTUM-First data with the hematology community and will initiate discussions with global regulatory authorities.”

The double-blind, placebo-controlled, phase 3 trial enrolled 539 patients with newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome or a myeloproliferative neoplasm and harbor a FLT3-ITD activating mutation in the bone marrow.2 Patients needed to be at least 18 years of age, have an ECOG performance status of 0 to 2, and acceptable renal and hepatic function.

If patients had a diagnosis of acute promyelocytic leukemia, AML secondary to prior chemotherapy or radiotherapy for other neoplasms, or they received prior treatment for AML, quizartinib or other FLT3-ITD inhibitors, or investigational agents or devices within 30 days before randomization, they were excluded.

Other exclusion criteria included a history of central nervous system leukemia; other malignancies except for adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated without evidence of disease for at least 2 years; uncontrolled or significant cardiovascular disease; acute or chronic systemic fungal, bacterial, or viral infection that is not well controlled; or clinically relevant liver disease, among others.

Study participants were randomized 1:1 to receive quizartinib or placebo in combination with standard anthracycline and cytarabine-based induction and consolidation regimens. Induction treatment comprised cytarabine and daunorubicin/idarubicin for up to 2 cycles, followed by quizartinib or placebo. Consolidation treatment included up to 4 cycles of cytarabine followed by quizartinib or placebo and/or hematopoietic stem cell transplant. Then, those who were eligible, including those who underwent transplantation, continued to receive quizartinib or placebo for up to 36 treatment cycles.

The primary end point of the study was OS, and key secondary end points included event-free survival, post-induction rates of complete remission (CR) and composite complete remission (CRc), and the percentage of patients who achieve CR or CRc with FLT3-ITD minimal residual disease negativity. Investigators also evaluated the safety and pharmacokinetics of the agent, along with exploratory efficacy and biomarker end points.

In June 2019, the Ministry of Health, Labor, and Welfare of Japan approved quizartinib (Vanflyta) for the treatment of adult patients with relapsed/refractory FLT3-ITD–positive AML, as detected by an approved assay.3 The decision was based on findings from the phase 3 QuANTUM-R trial (NCT02039726) and another phase 2 study.

In the same month and year, in the United States, the FDA issued a complete response letter to Daiichi Sankyo informing the company that its new drug application (NDA) would not be approved for quizartinib for use in this patient population.4 The decision followed an recommendation from the agency’s Oncologic Drug Advisory Committee in May 2019.5 The panel voted 8 to 3 that the available data with the agent did not definitively demonstrate that the benefit of its use outweighed any potential risks.

Data from QuANTUM-R showed that at a median follow-up of 23.5 months, the median OS with quizartinib was 6.2 months (95% CI, 5.3-7.2) vs 4.7 months (95% CI, 4.0-5.5) with salvage chemotherapy (HR, 0.76; 95% CI, 0.58-0.98; stratified log-rank test, 1-sided P = .0177).6 Findings from the FDA’s own efficacy analysis showed that the median OS in the investigative and control arms was 26.9 weeks (95% CI, 23.1-31.0) vs 20.4 weeks (95% CI, 17.0-25.2) with chemotherapy (HR, 0.77; 95% CI, 0.59-0.99; P = .019).

Several early-phase trials evaluating potential quizartinib combinations are underway at The University of Texas MD Anderson Cancer Center.


  1. Quizartinib added to chemotherapy demonstrates superior overall survival compared to chemotherapy alone in adult patients with newly diagnosed FLT3-ITD positive AML. News release. Daiichi Sankyo Company, Limited. November 18, 2021. Accessed November 19, 2021. https://bwnews.pr/3kV7K6C
  2. Quizartinib with standard of care chemotherapy and as continuation therapy in patients with newly diagnosed FLT3-ITD (+) acute myeloid leukemia (AML) (QuANTUM-First). ClinicalTrials.gov. Updated June 11, 2021. Accessed November 19, 2021. https://clinicaltrials.gov/ct2/show/NCT02668653