What is the difference between Quizatinib and Midostaurin?

Quizartinib and Midostaurin, as targeted therapies, play a key role in the treatment of acute myeloid leukemia (AML), especially patients with FLT3 mutations. Although these two drugs are both FLT3 tyrosine kinase inhibitors (FLT3-TKIs), they have significant differences in molecular structure, target selectivity, clinical application scenarios, efficacy differences, side effect profiles, and user populations. An in-depth understanding of these two drugs will help patients and doctors choose individualized treatment plans more scientifically.

First of all, from the perspective of target selectivity, quizartinib is a second-generationFLT3 inhibitor that is highly selective and mainly targets the FLT3-ITD mutant form. This mutated FLT3 is one of the most common genetic alterations in AML, and about 30% of AML patients carry this mutation. Quizartinib's affinity for FLT3-ITD is much higher than its inhibition of wild-type FLT3 (FLT3-WT). Therefore, while killing cancer cells, it has less inhibition on normal blood cells, helping to reduce side effects related to myelosuppression. Midostaurin is a first-generation multi-target tyrosine kinase inhibitor that, in addition to inhibiting FLT3, also inhibits KIT, PDGFR, VEGFR and other kinases. This broad spectrum makes it possible to produce more possible side effects during treatment and also increases the impact on non-tumor cells.

Secondly, in the clinical use stage, the indications of the two drugs are also different. Midostaurin was approved by the FDA as early as 2017 and can be used in combination with chemotherapy to treat newly diagnosed adult patients with FLT3 mutation-positive AML. Its main use scenario is to treat early-stage AML and can be used in combination with induction chemotherapy and consolidation therapy. Quizartinib is more focused on relapsed or refractory FLT3-ITD-positive AML and is a late-line treatment drug. In 2023, the US FDA approved quizartinib in combination with standard chemotherapy for adult patients with newly diagnosed FLT3-ITD AML, but the drug has not yet been officially launched in mainland China. In other words, midostaurin is currently more widely used around the world, especially in China, where it has been officially launched and has been included in the medical insurance list; while quizartinib has become increasingly prominent in international clinical studies and is considered to be a more potential precision targeted therapy drug.

In terms of efficacy, quizartinib has shown higher remission rates and longer disease-free survival in some studies due to its high selectivity and stronger inhibitory activity. Especially in relapsed/refractory patients, the efficacy advantage is more obvious. In contrast, midostaurin's efficacy may differ in some FLT3 mutation subtypes due to its insufficiently focused target. However, because midostaurin can be used in the induction and consolidation phases and works in combination with chemotherapy, it is still one of the first-line recommended options for patients with newly treated AML.

Side effects are another significant difference between the two drugs. Due to its multi-target mechanism, Midostaurin may cause a series of adverse reactions such as rash, gastrointestinal reactions, QT interval prolongation, musculoskeletal discomfort, and bone marrow suppression. One of the most common side effects of quizartinib is prolongation of the QT interval on the electrocardiogram. Others, such as nausea, fatigue, neutropenia, and elevated liver enzymes, also require close monitoring. Because quizartinib is a selective FLT3-ITD inhibitor with weak activity against FLT3-TKD mutations, combined or alternative medications may be needed in patients with multiple FLT3 mutations.

Reference materials:https://go.drugbank.com/drugs/DB12874