SCI
22 July 2024
Longitudinal Analyses of Circulating-Tumor DNA for Detection of EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Progression During Treatment: Data From FLAURA and AURA3
(JTO, IF: 21.0)
Gray JE, Markovets A, Reungwetwattana T, et al: Longitudinal Analyses of Circulating-Tumor DNA for Detection of EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Progression During Treatment: Data From FLAURA and AURA3. Journal of Thoracic Oncology , 2024
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-sensitizing and -resistance mutations may be detected in plasma via circulating tumor DNA (ctDNA). ctDNA level changes reflect alterations in tumor burden and could be a dynamic indicator of treatment effect. This analysis aimed to determine whether longitudinal EGFR-mutation ctDNA testing could detect progressive disease (PD) before radiologic detection.
表皮生长因子受体酪氨酸激酶抑制剂 (EGFR-TKI) 可通过循环肿瘤DNA（ctDNA）在血浆中检测到致敏和耐药突变。ctDNA水平变化反映了肿瘤负荷的变化，可作为治疗效果的动态指标。该分析旨在确定纵向EGFR突变ctDNA检测是否可以在放射学检测前检测疾病进展 (PD)。
This was a retrospective, exploratory ctDNA analysis in two phase 3 trials (FLAURA, NCT02296125; AURA3, NCT02151981). Patients had treatment-naïve (FLAURA) or EGFR-TKI pre-treated (AURA3) advanced non-small cell lung cancer (NSCLC) with EGFR mutations and on-study PD (RECIST), with a baseline ctDNA result and EGFR-mutation ctDNA monitoring beyond Cycle 3 Day 1. Patients received osimertinib versus comparator EGFR-TKIs (FLAURA) or chemotherapy (AURA3). Outcomes included time from ctDNA PD to RECIST PD, and to first subsequent treatment (FST; FLAURA only).
这是一项在两项III期试验 (FLAURA，NCT02296125；AURA3，NCT02151981) 中进行的回顾性、探索性ctDNA分析。患者为初治（FLAURA）或EGFR-TKI预治疗（AURA3）EGFR 突变的晚期非小细胞肺癌（NSCLC）患者，且为研究期间PD（RECIST）患者，具有基线ctDNA结果和第3周期第1天后的EGFR突变ctDNA监测结果。患者接受奥希替尼与对照药物EGFR-TKI（FLAURA）或化疗（AURA3）。结局包括从ctDNA PD至RECIST PD和首次后续治疗的时间（FST；仅FLAURA）。
ctDNA PD preceded/co-occurred with RECIST-defined PD in 93/146 (64%) patients in FLAURA and 82/146 (56%) in AURA3. Median time from ctDNA PD to RECIST-defined PD (months) was 3.4 and 2.6 in the osimertinib and comparator EGFR-TKI arms (FLAURA) and 2.8 and 1.5 in the osimertinib and chemotherapy arms (AURA3). In FLAURA, median time from ctDNA PD to FST (months) was 6.0 and 4.7 in the osimertinib (n = 51) and comparator EGFR-TKI arms (n = 70).
FLAURA中93/146(64%) 例患者和 AURA3 中82/146(56%) 例患者的 ctDNA PD 先于/同时发生 RECIST 定义的PD。奥希替尼和对照药物 EGFR-TKI 组 (FLAURA) 从 ctDNA PD 至 RECIST 定义的 PD 的中位时间（月）分别为3.4和2.6，奥希替尼和化疗组 (AURA3) 分别为2.8和1.5。在 FLAURA 中，奥希替尼 (n = 51) 和对照药物 EGFR-TKI 组 (n = 70) 从 ctDNA PD 至 FST 的中位时间（月）分别为6.0和4.7。
Among patients with EGFR mutation-positive advanced NSCLC receiving EGFR-TKI or chemotherapy with ctDNA data and RECIST-defined PD, ctDNA PD preceded/co-occurred with RECIST-defined PD in approximately 60% of cases. Longitudinal ctDNA monitoring may detect PD before radiologic PD.
在接受 EGFR-TKI 或化疗的 EGFR 突变阳性晚期 NSCLC 患者中，有 ctDNA 数据和 RECIST 定义的PD，约60%的病例 ctDNA PD 先于/同时发生 RECIST 定义的PD。纵向 ctDNA 监测可在放射学 PD 前检测PD。
