Jiang Yu, Lin Yuechun, Fu Wenhai, He Qihua, Liang Hengrui, Zhong Ran, Cheng Ran, Li Bingliang, Wen Yaokai, Wang Huiting, Li Jianfu, Li Caichen, Xiong Shan, Chen Songan, Xiang Jianxing, Mann Michael J, He Jianxing, Liang Wenhua
National Clinical Research Center for Respiratory Disease, Guangzhou, China.
Departments of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
EClinicalMedicine. 2023 Sep 14;64:102205. doi: 10.1016/j.eclinm.2023.102205. eCollection 2023 Oct.
Currently, the role of EGFR-TKIs as adjuvant therapy for stage I, especially IA NSCLC, after surgical resection remains unclear. We aimed to compare the effect of adjuvant EGFR-TKIs with observation in such patients by incorporating an established 14-gene molecular assay for risk stratification.
This retrospective cohort study was conducted at the First Affiliated Hospital of Guangzhou Medical University (Study ID: ChNCRCRD-2022-GZ01). From March 2013 to February 2019, completely resected stage I NSCLC (8th TNM staging) patients with sensitive EGFR mutation were included. Patients with eligible samples for molecular risk stratification were subjected to the 14-gene prognostic assay. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics.
A total of 227 stage I NSCLC patients were enrolled, with 55 in EGFR-TKI group and 172 in the observation group. The median duration of follow-up was 78.4 months. After IPTW, the 5-year DFS (HR = 0.30, 95% CI, 0.14-0.67; P = 0.003) and OS (HR = 0.26, 95% CI, 0.07-0.96; P = 0.044) of the EGFR-TKI group were significantly better than the observation group. For subgroup analyses, adjuvant EGFR-TKIs were associated with favorable 5-year DFS rates in both IA (100.0% vs. 84.5%; P = 0.007), and IB group (98.8% vs. 75.3%; P = 0.008). The 14-gene assay was performed in 180 patients. Among intermediate-high-risk patients, EGFR-TKIs were associated with a significant improvement in 5-year DFS rates compared to observation (96.0% vs. 70.5%; P = 0.012), while no difference was found in low-risk patients (100.0% vs. 94.9%; P = 0.360).
Our study suggested that adjuvant EGFR-TKI might improve DFS and OS of stage IA and IB EGFR-mutated NSCLC, and the 14-gene molecular assay could help patients that would benefit the most from treatment.
This work was supported by China National Science Foundation (82022048, 82373121).
目前，表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）作为Ⅰ期，尤其是ⅠA期非小细胞肺癌（NSCLC）手术切除后辅助治疗的作用仍不明确。我们旨在通过纳入一种成熟的14基因分子检测方法进行风险分层，比较辅助性EGFR-TKIs与观察等待在这类患者中的效果。
这项回顾性队列研究在广州医科大学附属第一医院开展（研究编号：ChNCRCRD-2022-GZ01）。纳入2013年3月至2019年2月间完全切除的Ⅰ期NSCLC（第8版TNM分期）且表皮生长因子受体（EGFR）敏感突变的患者。有符合分子风险分层检测标准样本的患者接受14基因预后检测。采用治疗权重逆概率法（IPTW）以尽量减少基线特征的不平衡。
共纳入227例Ⅰ期NSCLC患者，其中EGFR-TKI组55例，观察等待组172例。中位随访时间为78.4个月。IPTW后，EGFR-TKI组的5年无病生存率（HR = 0.30，95%CI：0.14 - 0.67；P = 0.003）和总生存率（HR = 0.26，95%CI：0.07 - 0.96；P = 0.044）显著优于观察等待组。亚组分析显示，辅助性EGFR-TKIs在ⅠA期（100.0% 对84.5%；P = 0.007）和ⅠB期（98.8% 对75.3%；P = 0.008）患者中均与良好的5年无病生存率相关。180例患者进行了14基因检测。在中高危患者中，与观察等待相比，EGFR-TKIs与5年无病生存率显著提高相关（96.0% 对70.5%；P = 0.012），而在低危患者中未发现差异（100.0% 对94.9%；P = 0.360）。
我们的研究表明，辅助性EGFR-TKI可能改善ⅠA期和ⅠB期EGFR突变NSCLC患者的无病生存率和总生存率，且14基因分子检测有助于识别最能从治疗中获益的患者。
本研究得到国家自然科学基金（82022048，82373121）的支持。
