Adjuvant chemotherapy for stage IA-IIA non-squamous, non-small-cell lung cancer identified as molecular high-risk by a 14-gene expression profile (AIM-HIGH): an international, randomised, phase 3 trial.

Current guidelines recommend adjuvant treatment for patients considered to be at high risk in stages IB and IIA, but suggest criteria that have not been validated to predict benefit.

当前指南建议对IB期和IIA期被认为高风险的患者进行辅助治疗，但建议的标准尚未得到验证以预测获益。

A previously validated, CLIA-certified 14-gene expression profile has identified patients with high-risk non-squamous NSCLC tumours in stages IA-IIA who benefitted from adjuvant chemotherapy in a non-randomised prospective study.

一项先前经过验证并获得CLIA认证的14基因表达谱在一项非随机前瞻性研究中识别出IA-IIA期高危非鳞状NSCLC肿瘤患者，这些患者从辅助化疗中受益。

In this prespecified interim analysis, we aimed to assess the efficacy and safety of platinum-based adjuvant chemotherapy in patients with stage IA-IIA molecular high-risk non-squamous NSCLC in a randomised trial.

在这项预先设定的中期分析中，我们的目标是评估IA-IIA期分子高危非鳞状NSCLC患者在随机试验中接受基于铂类的辅助化疗的疗效和安全性。

Methods

AIM-HIGH, a randomised, phase 3 trial, was done at 45 centres in France, Germany, and the USA.

AIM-HIGH是一项随机、III期试验，在法国、德国和美国的45个中心进行。

Patients aged 18 years or older with stage IA-IIA non-squamous NSCLC, an adequate tumour sample, and an Eastern Cooperative Oncology Group performance status of 0-1 underwent risk stratification with the 14-gene assay.

年龄在18岁或以上的患者，患有IA-IIA期非鳞状非小细胞肺癌（NSCLC），拥有足够的肿瘤样本，并且东部肿瘤协作组（Eastern Cooperative Oncology Group）的体能状态评分为0-1，这些患者使用14基因检测进行了风险分层。

Patients with a molecular high risk, defined as those receiving a high-risk or an intermediate-risk score, were randomly assigned (1:1) to four cycles of platinum-based adjuvant chemotherapy (using local institutional standard of care regimens) or observation.

被定义为接受高风险或中等风险评分的患者，被随机分配（1:1）接受四周期的基于铂类的辅助化疗（使用当地机构的标准治疗方案）或观察。

Randomisation was stratified according to age, sex, and tumour size of 4 cm or more.

随机分配根据年龄、性别和肿瘤大小4厘米或更大进行分层。

The primary outcomes for the study and for this prespecified interim analysis were 48-month and 24-month disease-free survival, respectively, in the modified intention-to-treat(mITT) population, which was defined as randomly assigned patients who continued to meet eligibility criteria either at chemotherapy initiation or at random assignment to observation; an early interim analysis was prespecified to detect a large difference between groups.

该研究的主要结果以及此次预定的中期分析结果分别是，修改意向治疗(mITT)人群中的48个月和24个月无病生存率。mITT人群被定义为随机分配的患者，他们在化疗开始或随机分配至观察时仍然符合资格标准；预定的早期中期分析旨在检测两组之间的显著差异。

This trial is registered at ClinicalTrials.gov, NCT01817192, and is closed to enrolment.

该试验已在ClinicalTrials.gov上注册，注册号为NCT01817192，并已停止招募。

Results

Between Sept 11, 2020, and Feb 7, 2025, 449 patients were enrolled and underwent risk stratification. 236 patients with molecular high risk were randomly assigned to chemotherapy (n=124) or observation (n=112).

在2020年9月11日至2025年2月7日期间，共有449名患者被纳入研究并进行了风险分层。其中236名分子高风险患者被随机分配至化疗组(n=124)或观察组(n=112)。

At the time of the prespecified interim analysis, 87 patients were evaluable in the mITT population (47 [54%] males and 40 [46%] females; median age 63 years [IQR 52-74]) in the chemotherapy group and 107 (58 [54%] males and 49 [46%] females; 66 years [56-76]) in the observation group. 48 (55%) patients in the chemotherapy group and 58 (54%) patients in the observation group had stage IA disease; 34 (39%) and 44 (41%), respectively, had stage IB disease, and five (6%) and five (5%), respectively, had stage IIA disease.

在预定的中期分析时点，mITT人群中87名患者可评估（化疗组47名[54%]男性和40名[46%]女性；中位年龄63岁[四分位数间距52-74]），观察组107名（58名[54%]男性和49名[46%]女性；中位年龄66岁[四分位数间距56-76]）。化疗组中有48名（55%）患者和观察组中有58名（54%）患者患有IA期疾病；化疗组中有34名（39%）和观察组中有44名（41%）患者患有IB期疾病，化疗组和观察组各有5名（6%和5%）患者患有IIA期疾病。

Six (3%) of 200 patients in the mITT population had died at the time of the interim analysis. 24-month disease-free survival was 96% (95% CI 92-100) with adjuvant chemotherapy versus 79% (70-90) with observation (hazard ratio0·22 [0·06-0·76]; p=0·0087).

在中期分析时，200名mITT人群中已有6名（3%）患者死亡。辅助化疗组的24个月无病生存率为96%（95%置信区间92-100），而观察组为79%（70-90）（风险比0·22 [0·06-0·76]；p=0·0087）。

interpretation

The 14-gene assay identified patients with molecular high risk who benefitted from adjuvant chemotherapy.

14基因检测识别出那些从辅助化疗中获益的分子高风险患者。

Use of the assay to determine eligibility for adjuvant therapy in stage IA-IIA non-squamous NSCLC has the potential to substantially improve otherwise persistently poor outcomes.

在IA-IIA期非鳞状非小细胞肺癌中，使用该检测方法来确定辅助治疗的适应症有可能显著改善持续不良的治疗结果。

funding

Razor Genomics.

Razor Genomics公司。