Quizartinib clinical trial introduction

Quizatinib, an anti-cancer drug targeting a specific type of acute myeloid leukemia (AML), is mainly used to treat adult patients who are FLT3-ITD positive. This drug is particularly suitable for patients whose disease has relapsed or failed to respond to previous treatments, and for patients who require continued treatment after hematopoietic stem cell transplantation (HSCT).

In a clinical trial calledQuANTUM-First (NCT02668653), researchers 539patients newly diagnosed with FLT3-ITDpositiveAML were studied in depth. This is a randomized, double-blind, placebo-controlled study designed to evaluate the effect of quizartinib (VANFLYTA) in combination with standard chemotherapy.

Prior to the trial, investigators prospectively determined patients' FLT3-ITD status and performed retrospective validation using the FDA-approved LeukoStrat® CDx FLT3 mutation test. Patients were stratified by age, white blood cell count at diagnosis, and region and randomly assigned to VANFLYTA (n=268) or placebo (n=271).

All patients received combined induction and consolidation therapy and maintenance monotherapy according to initial assignment. Treatment consists of an induction phase of a 7+3 regimen (cytarabine plus daunorubicin or idarubicin), followed by oral treatment with VANFLYTA or placebo, and an optional second induction and high-dose cytarabine treatment. After the consolidation treatment phase, patients enter maintenance treatment for up to 36 cycles of 28 days.

Baseline demographics and disease characteristics were well balanced between the two groups. The median age of patients was 56 years, and characteristics such as gender, race, and performance status were evenly distributed. Most patients had intermediate-risk cytogenetic features, whereasFLT3-ITDVariant allele frequencies vary between patients.

During the course of treatment, 20% of patients received a second round of induction therapy, 65% of patients started at least one round of consolidation therapy, and 39% of patients entered the maintenance treatment phase. It is worth noting that among patients who entered maintenance therapy, a considerable number of patients completed at least 12 or more cycles of treatment. In addition, approximately 29%of patients received HSCT after first complete remission (CR).

In terms of efficacy, the study mainly focused on the key indicator of overall survival (OS). After at least 24 months of follow-up, the results showed a statistically significant improvement in OS in the VANFLYTA group, with a hazard ratio (HR) of 0.78. Especially in the subgroup of patients who continued to receive maintenance therapy with VANFLYTA after consolidation chemotherapy, the improvement in OS was more significant (HR=0.40). However, the difference in OS was less pronounced among patients who received maintenance therapy with VANFLYTA or placebo after HSCT.

In addition, the VANFLYTA group was comparable to the placebo group in terms of complete response rate (CR rate), but The median duration of CR was significantly longer in the VANFLYTA group (38.6 months vs. 12.4 months).

In summary, quizartinib (VANFLYTA) has demonstrated good efficacy and safety in the treatment of FLT3-ITDpositive AML, especially in combination with standard chemotherapy and maintenance treatment. This research result provides new treatment options and hope for such patients.

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Reference: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=29cdbcfe-497d-4e78-bb7b-2d4acafe8e86