The phase 3 COMMODORE trial evaluated gilteritinib versus salvage chemotherapy (SC) in a predominantly Asian relapsed/refractory (R/R) FLT3-mutated (FLT3^mut+) acute myeloid leukemia (AML) patient population. The primary endpoint was overall survival (OS); secondary endpoints included event-free survival (EFS) and complete remission (CR) rate. As of June 30, 2020 (interim analysis: 32.2 months after study initiation), 234 patients were randomized (gilteritinib, n = 116; SC, n = 118). Median OS was significantly longer with gilteritinib versus SC (9.6 vs. 5.0 months; HR 0.566 [95% CI: 0.392, 0.818]; p = 0.00211) with a median follow-up of 10.3 months. Median EFS was also significantly longer with gilteritinib (2.8 vs. 0.6 months; HR 0.551 [95% CI: 0.395, 0.769]; p = 0.00004). CR rates with gilteritinib and SC were 16.4% and 10.2%, respectively; composite CR rates were 50.0% and 20.3%, respectively. Exposure-adjusted grade ≥3 adverse event (AE) rates were lower with gilteritinib (58.38 events/patient-year [E/PY]) versus SC (168.30 E/PY). Common AEs with gilteritinib were anemia (77.9%) and thrombocytopenia (45.1%). Gilteritinib plasma concentration peaked ~4 h postdose; ~3-fold accumulation occurred with multiple dosing. The COMMODORE trial demonstrated that gilteritinib significantly improved OS and EFS in predominantly Asian patients, validating the outcomes of gilteritinib from the ADMIRAL trial in R/R FLT3^mut+ AML.

3 期 COMMODORE 试验在以亚洲复发/难治性 （R/R） FLT3 突变 （FLT3^mut+） 急性髓系白血病 （AML） 患者群体中评估了吉替替尼与挽救性化疗 （SC） 的疗效。主要终点是总生存期 （OS）;次要终点包括无事件生存期 （EFS） 和完全缓解 （CR） 率。截至 2020 年 6 月 30 日（中期分析：研究开始后 32.2 个月），234 名患者被随机分配（gilteritinib，n = 116; SC， n = 118）。吉替替尼组的中位 OS 显著延长至 SC 组 （9.6 vs. 5.0 个月;HR 0.566 [95% CI： 0.392， 0.818];p = 0.00211），中位随访时间为 10.3 个月。吉替替尼组的中位 EFS 也显著更长 （2.8 vs. 0.6 个月;HR 0.551 [95% CI： 0.395， 0.769];p = 0.00004）。吉替替尼和 SC 的 CR 率分别为 16.4% 和 10.2%;综合 CR 率分别为 50.0% 和 20.3%。吉特替尼 （58.38 事件/患者年 [E/PY]） （58.38 事件/患者年 [E/PY]） 的暴露调整后 ≥ 级不良事件 （AE） 发生率低于 SC （168.30 E/PY）。吉特替尼的常见 AE 是贫血 （77.9%） 和血小板减少症 （45.1%）。吉替替尼血浆浓度在给药后 ~4 小时达到峰值;多次给药时发生 ~3 倍的积累。COMMODORE 试验表明，吉替替尼显著改善了以亚洲为主的患者的 OS 和 EFS，验证了吉替替尼在 R/R FLT3^mut+ AML 中的 ADMIRAL 试验的结果。