Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial.

Aumolertinib, a third-generation EGFR tyrosine-kinase inhibitor, is approved in China for adjuvant treatment in patients with NSCLC harbouring EGFR with an exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation.

奥美替尼，一种第三代EGFR酪氨酸激酶抑制剂，在中国被批准用于携带EGFR 19号外显子缺失（ex19del）或21号外显子替换（Leu858Arg）突变的非小细胞肺癌患者的辅助治疗。

The ARTS study aimed to evaluate the efficacy and safety of adjuvant therapy with aumolertinib in patients with stage II-IIIB EGFR-mutated NSCLC.

ARTS 研究旨在评估在 II-IIIB 期 EGFR 突变型非小细胞肺癌患者中使用奥莫替尼作为辅助治疗的疗效和安全性。

Methods

This double-blind, multicentre, randomised, controlled, phase 3 trial enrolled patients from 48 hospitals in mainland China.

这是一项双盲、多中心、随机、对照的 III 期临床试验，招募了来自中国大陆 48 家医院的患者。

Eligible patients were 18 years or older with stage II-IIIB NSCLC, had undergone a complete resection followed by standard adjuvant therapy, and had an EGFR ex19del or Leu858Arg mutation and an Eastern Cooperative Oncology Group performance status score of 0 or 1.

符合条件的患者年龄在18岁或以上，患有II-IIIB期非小细胞肺癌（NSCLC），已经接受了完全切除手术并进行了标准的辅助治疗，且存在EGFR外显子19缺失（ex19del）或Leu858Arg突变，并且东部肿瘤协作组（Eastern Cooperative Oncology Group）的体能状态评分为0或1。

Patients were stratified by EGFR mutation status and tumour stage and were randomly assigned (1:1) to receive aumolertinib 110 mg or placebo orally, once daily for 3 years or until disease recurrence or other discontinuation criteria were met.

患者根据EGFR突变状态和肿瘤分期进行分层，并按1:1的比例随机分配，接受每日一次口服110 mg的奥美替尼或安慰剂，持续3年或直至疾病复发或满足其他停药标准。

Patients were randomly allocated to groups using an interactive web response system; the double‑dummy technique masked patients, investigators, and assessors.

患者通过交互式网络响应系统随机分配到各组；双盲法对患者、研究者和评估者进行了掩盖。

The primary endpoint was disease-free survival in the modified intention-to treat (mITT) population (ie, all patients with stage II-IIIB NSCLC harbouring EGFR mutations who had undergone complete tumour resection and standard adjuvant therapy), assessed by blinded independent central review (BICR).

主要终点是改良意向治疗(mITT)人群中的无病生存期（即所有II-IIIB期NSCLC携带EGFR突变并已接受完全肿瘤切除和标准辅助治疗的患者），通过盲法独立中心审查(BICR)进行评估。

Safety was assessed in all patients who received at least one dose of study treatment.

所有接受至少一剂研究治疗的患者均进行了安全性评估。

Although the study is ongoing, with some patients remaining in follow-up, this analysis represents the protocol-specified primary analysis.

尽管研究仍在进行中，部分患者仍在随访中，但本次分析代表了协议规定的初步主要分析。

This study is registered with ClinicalTrials.gov (NCT04687241).

该研究已在ClinicalTrials.gov注册（NCT04687241）。

Results

Between April 30, 2021, and May 17, 2022, 399 individuals were screened for study eligibility; of these, 214 patients were randomly assigned to receive aumolertinib or placebo (107 in each group). 120 (56%) patients were female, 94 (44%) were male, median age was 59 years (IQR 54-66), and all patients were Chinese. 204 (95%) of 214 patients had received prior adjuvant chemotherapy.

2021年4月30日至2022年5月17日之间，共有399名个体接受了研究资格筛查；其中，214名患者被随机分配接受奥莫替尼或安慰剂治疗（每组各107名）。

One patient in the aumolertinib group and three patients in the placebo group had stage I disease; therefore, 106 patients in the aumolertinib group and 104 in the placebo group were included in the mITT (primary analysis) population.

在奥莫乐替尼组有一名患者和安慰剂组有三名患者患有I期疾病；因此，奥莫乐替尼组有106名患者和安慰剂组有104名患者被纳入mITT（主要分析）人群。

As of the data cutoff date (April 15, 2024), the median duration of follow-up was 27·56 months (IQR 22·18-27·70) in the aumolertinib group and 27·63 months (22·18-27·79) in the placebo group.

截至数据截止日期（2024年4月15日），奥莫乐替尼组的中位随访时间为27.56个月（四分位数间距22.18-27.70），安慰剂组为27.63个月（四分位数间距22.18-27.79）。

The BICR-assessed disease-free survival was significantly improved in the aumolertinib group compared with the placebo group, with an HR of 0·17 (95% CI 0·09-0·29, p<0·0001).

通过BICR评估的无病生存期在奥莫乐替尼组与安慰剂组相比有显著改善，风险比为0.17（95%置信区间0.09-0.29，p<0.0001）。

The median disease-free survival per BICR in the aumolertinib group was not reached (95% CI 29·14 to not applicable), whereas it was 19·42 months (11·24-26·22) in the placebo group.

根据BICR评估，奥莫乐替尼组的中位无病生存期未达到（95%置信区间29.14至不适用），而安慰剂组为19.42个月（11.24-26.22）。

The most common grade 3-4 adverse events in the aumolertinib group versus the placebo group were increased blood creatine phosphokinase (seven [7%] vs none), prolonged electrocardiogram QT interval (three [3%] vs three [3%]), hypertension (one [1%] vs five [5%]), and pneumonia (two [2%] vs three [3%]).

在奥莫乐替尼组与安慰剂组中，最常见的3-4级不良事件分别是血清肌酸激酶增加（七例[7%]对比无），心电图QT间期延长（三例[3%]对比三例[3%]），高血压（一例[1%]对比五例[5%]）和肺炎（两例[2%]对比三例[3%]）。

Treatment-related serious adverse events occurred in one (1%) patient receiving aumolertinib and three (3%) patients receiving placebo.

与治疗相关的严重不良事件发生在一名（1%）接受奥莫乐替尼治疗的患者和三名（3%）接受安慰剂治疗的患者中。

No treatment-related deaths occurred and no new safety signals were identified for aumolertinib.

未发生与治疗相关的死亡事件，且未发现新的安全信号。

interpretation

Aumolertinib showed substantial clinical benefits as adjuvant therapy in Chinese patients with stage II-IIIB EGFR-mutated NSCLC.

在II-IIIB期EGFR突变型非小细胞肺癌的中国患者中，奥美替尼作为辅助治疗显示出显著的临床益处。

The manageable safety profile of aumolertinib supports its suitability in the adjuvant setting.

奥莫替尼良好的安全性特征支持其在辅助治疗中的适用性。

funding

Hansoh Pharmaceutical Group.

翰森制药集团。

translation

For the Chinese translation of the abstract see Supplementary Materials section.

摘要的中文翻译请参见补充材料部分。