How effective is Quizartinib treatment?

On July 20, 2023, the U.S. Food and Drug Administration (FDA) officially approved quizartinib (quizartinib, trade nameVanflyta, manufactured by Daiichi Sankyo Co., Ltd.) with standard cytarabine and anthracycline induction therapy, cytarabine consolidation therapy, and as maintenance monotherapy after consolidation chemotherapy for newly diagnosed patients with FLT3 Adult patients with pan>internal tandem duplication (ITD)-positive acute myeloid leukemia (AML). This approval is based on rigorous clinical trial results and provides a new treatment option for patients with AML.

QuANTUM-First(NCT02668653) is a pivotal randomized, double-blind, placebo-controlled trial that included 539patients newly diagnosed with FLT3-ITDpositiveAML. The trial uses prospective clinical trial testing to determine FLT3-ITD status and retrospective validation with companion diagnostic LeukoStrat CDx FLT3 mutation testing. Patients were randomly assigned to the quizartinib group (n=268) or the placebo group (n=271) in a 1:1 ratio, and received corresponding induction, consolidation therapy and maintenance monotherapy. Of note, patients were not rerandomized after initiation of consolidation therapy, whereas patients who received hematopoietic stem cell transplantation (HSCT) began maintenance therapy after recovery from HSCT.

The trial's primary efficacy outcome measure is overall survival (OS), which is the time from the date of randomization to death from any cause. After at least 24 months of follow-up, the primary analysis showed a statistically significant improvement in OS in the quizartinib group, with a risk The hazard ratio (HR) is 0.78, 95%The confidence interval (CI) is 0.62 to 0.98, and the two-sided p value is 0.0324. In addition, the complete response (CR) rate in the quizartinib group was 55% and the median duration was 38.6 months, while the CR rate in the placebo group was also 55%, but the median duration was only 12.4 months. However, it should be noted that quizartinib is not indicated as maintenance monotherapy after allogeneic HSCT, as the use of quizartinib has not been shown to improve OS in this setting.

Although quizartinib has demonstrated significant therapeutic effects, its use is also associated with certain risks. The black box warning states that the drug may cause serious heart problems such as QT prolongation, torsade de pointes, and cardiac arrest. Therefore, quizartinib is only available through a restricted program called Vanflyta REMS under Risk Assessment and Mitigation Strategies (REMS) to ensure patient safety during use.

Regarding the medication regimen of quizartinib, the recommended dosage is as follows: During induction therapy, 35.4mg orally administered daily, on days 8-21“7+3”program; during consolidation treatment, take orally every day on days 6-1935.4mg; during maintenance treatment, take orally every day from 1 to 1426. 5mg, followed by 53mg orally daily thereafter for up to thirty-six 28 day cycles.

In summary, the approval of quizartinib provides new treatment hope for FLT3-ITDpositiveAML patients. However, during use, doctors and patients need to pay close attention to its potential cardiac risks and follow a strict medication regimen to ensure the safety and effectiveness of the treatment.

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Reference: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-quizartinib-newly-diagnosed-acute-myeloid-leukemia