AENEAS 阿美替尼对比吉非替尼作为一线治疗EGFR19del或L858R突变的局晚期或转移性非小细胞肺癌的随机III期研究

SCI

18 MAy 2022

AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or Metastatic Non–Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations 

（JCO, IF: 44.5）

• Lu S, Dong X, Jian H, et al. AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon–Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations. Journal of Clinical Oncology;0:JCO.21.02641.

• Corresponding Author：Shun Lu, MD, Department of Medical Oncology, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, China; e-mail: shunlu@sjtu.edu.cn.

PURPOSE  目的

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR- mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768).

Aumolertinib（阿美替尼，原almonertinib；HS-10296）是一种在中国获批的新型第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）。这项双盲 III 期试验评估了阿美替尼与吉非替尼作为一线药治疗局部晚期或转移性EGFR突变的非小细胞肺癌（NSCLC）的疗效和安全性对比。（ClinicalTrials.gov 注册号：NCT03849768）

METHODS 方法

Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment.

在中国53个试验中心的患者被随机按1:1分配，每日一次接受阿美替尼(110 mg)或吉非替尼(250 mg)。研究者评估的主要终点是无进展生存期(PFS)。

RESULTS 结果

A total of 429 patients who were naive to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P, .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). 

共有429名未接受治疗的局部晚期或转移性NSCLC患者参加了试验。阿美替尼组的PFS明显长于吉非替尼组(风险比，0.46;95% CI, 0.36 ~ 0.60;P<0.0001)。阿美替尼组的中位PFS为19.3个月(95% CI, 17.8 - 20.8)，吉非替尼组为9.9个月(95% CI, 8.3 - 12.6)。阿美替尼组和吉非替尼组的客观缓解率和疾病控制率相似(客观缓解率分别为73.8%和72.1%; 疾病控制率分别为93.0%和96.7%)。

The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade $ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively.

阿美替尼的中位缓解维持期为18.1个月(95% CI, 15.2至未及)，吉非替尼的中位缓解维持期为8.3个月(95% CI, 6.9至11.1)。在阿美替尼组和吉非替尼组中，分别有36.4%和35.8%的患者出现了3级(任何原因)不良事件。服用阿美替尼的患者中有23.4%和16.4%出现皮疹和腹泻(任何程度)，而服用吉非替尼的患者中分别为41.4%和35.8%。

CONCLUSIONS 结论

Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.

阿美替尼是一种耐受良好的第三代EGFR-TKI药物，可作为EGFR突变的NSCLC一线治疗的一种选择。