Dong Song, Yan Bingfa, Liu Si-Yang, Gao Xuan, Hong Hui-Zhao, Li Hong-Ji, Gao Wei, Yan Hong-Hong, Maggie Liu Si-Yang, Tu Hai-Yan, Pan Yi, Zhou Qing, Yang Xue-Ning, Xia Xue-Feng, Yi Xin, Zhong Wen-Zhao, Wu Yi-Long, Zhang Jia-Tao
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Geneplus-Beijing Institute, Beijing, People's Republic of China.
JTO Clin Res Rep. 2024 Nov 2;6(1):100758. doi: 10.1016/j.jtocrr.2024.100758. eCollection 2025 Jan.
EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA -mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation.
From January 2019 to December 2022, 71 patients with stages I to III NSCLC and (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group.
Overall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post-EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0-35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission.
Our initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）是IB至IIIA期表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的标准辅助治疗方法。然而，采用这种方法纳入分子残留疾病（MRD）引导的降阶梯策略值得进一步研究。
2019年1月至2022年12月，71例I至III期NSCLC且有EGFR（外显子19缺失或L858R）突变的患者纳入本观察性研究。使用MRD_Navigator检测法分析了共375份血样。其中，27例患者基于未检测到MRD而暂停EGFR-TKI治疗，因此被纳入适应性降阶梯组。
总体而言，纵向MRD的敏感性为86.2%。仅4例患者（11.8%）在纵向MRD未检测到时复发，阴性预测值为88.2%。术后MRD可检测到的患者中，9例随后接受了EGFR-TKI治疗，EGFR-TKI治疗后仅1例（11.1%）实现了循环肿瘤DNA持续清除。此外，22例IB至III期疾病患者此前基于未检测到MRD而暂停TKI治疗，被纳入适应性组，TKI平均使用时长为3.9（范围：0至35.0）个月。这22例患者的2年无病生存率为80.2%，中位数未达到。5例患者（22例中的5例，22.7%）在停药期间疾病复发，但在EGFR-TKI治疗下直至最近一次随访时病情稳定。2例患者仍处于完全缓解状态。
我们的初步研究结果强调了基于循环肿瘤DNA-MRD监测的EGFR-TKI辅助治疗适应性降阶梯方法的潜力。
