Quizartinib for Newly Diagnosed FLT3-Internal Tandem Duplication-Negative AML: The Randomized, Double-Blind, Placebo-Controlled, Phase II QUIWI Study.

The phase III QuANTUM-First trial showed that quizartinib significantly prolonged survival versus placebo when added to standard chemotherapy, followed by single-agent maintenance, in patients with newly diagnosed (ND) FLT3-ITD-positive AML.

第三阶段QuANTUM-First试验显示，当Quizartinib与标准化疗联合使用，随后进行单药维持治疗时，与安慰剂相比，显著延长了新诊断（ND）FLT3-ITD阳性AML患者的生存期。

We investigated the safety and efficacy of quizartinib in patients with ND FLT3-ITD-negative AML.

我们研究了quizartinib在无复发生存期FLT3-ITD阴性急性髓细胞性白血病（AML）患者中的安全性和疗效。

Methods

The phase II, randomized, double-blind, placebo-controlledQUIWI trial enrolled patients age 18-70 years with ND FLT3-ITD-negative (mutant-to-WT allelic ratio <0.03) AML.

II期、随机、双盲、安慰剂对照的QUIWI试验招募了年龄在18-70岁之间的无复发生存期FLT3-ITD阴性（突变与野生型等位基因比率小于0.03）急性髓细胞性白血病（AML）患者。

Patients were randomly assigned 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg once daily or placebo, followed by single-agent maintenance with quizartinib or placebo.

患者按2:1的比例随机分配接受标准诱导和巩固化疗，同时每天一次服用60 mg的quizartinib或安慰剂，随后进行quizartinib或安慰剂的单一药物维持治疗。

The primary end point was event-free survival (EFS).

主要终点事件是无事件生存（EFS）。

Secondary end points included overall survival(OS) and safety.

次要终点包括总生存（OS）和安全性。

Results

Overall, 273 patients were randomly assigned to quizartinib (n = 180) or placebo (n = 93).

总体而言，273名患者被随机分配接受Quizartinib治疗（n=180）或安慰剂（n=93）。

At data cutoff, median EFS was 20.4 months and 9.9 months in the quizartinib and placebo arms, respectively (P = .046).

在数据截止时，quizartinib组和安慰剂组的中位无进展生存期（EFS）分别为20.4个月和9.9个月（P = .046）。

Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively (P = .012); 3-year OS rates were 60.8% and 45.7%.

在quizartinib组和安慰剂组中，中位总生存期（OS）尚未达到和29.3个月（P = .012）；3年总生存率分别为60.8%和45.7%。

The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis.

报告最多的不良事件（任何级别）是发热、皮疹、腹泻和粘膜炎。

Conclusions

The addition of quizartinib to standard chemotherapy was associated with significantly longer EFS and OS than placebo in patients with ND FLT3-ITD-negative AML.

在FLT3-ITD阴性的ND AML患者中，将quizartinib加入标准化疗比安慰剂显著延长了无进展生存期（EFS）和总生存期（OS）。