Laboratoire de Biologie Moléculaire, Hôpital de Hautepierre, Strasbourg, France; Unité INSERM U1113, Streinth Lab, Strasbourg, France; Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, France.
Service de Biostatistique et d'Epidémiologie, Gustave-Roussy, Villejuif, France.
Clin Lung Cancer. 2019 May;20(3):222-230. doi: 10.1016/j.cllc.2018.12.012. Epub 2018 Dec 19.
Evaluation of EGFR Mutation status for the administration of EGFR-TKIs in non-small cell lung Carcinoma (ERMETIC) was a prospective study designed to validate the prognostic value of EGFR/KRAS mutations in patients with advanced non-small-cell lung cancer (NSCLC), all receiving a first-generation tyrosine kinase inhibitor, erlotinib. ERMETIC2 was an ancillary project evaluating the clinical value of common EGFR/KRAS-mutated subclones regarding prognosis using highly sensitive molecular detection methods.
Tumor samples from 228 patients with NSCLC (59% adenocarcinoma, 37% women, and 19% never/former smokers) were available for reanalysis using alternative highly sensitive molecular techniques. A multivariate Cox model was used for prognostic analysis.
Using alternative highly sensitive techniques, 16 EGFR and 51 KRAS supplementary mutations were newly identified, all still exclusive, leading to an overall rate of 12.3% (n = 28) and 33.3% (n = 76), respectively. Using real-time polymerase chain reaction (hybridization probe), they were significantly associated with progression-free survival (P = .02) and overall survival (OS) (P = .01), which were better for EGFR-mutated patients for progression-free survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.28-0.78) and OS (HR, 0.56; 95% CI, 0.31-1), and worse for KRAS mutations and OS (HR, 1.63; 95% CI, 1.09-2.44). Using the most sensitive technique detection for KRAS-clamp polymerase chain reaction-KRAS mutated subclones did not impact OS.
KRAS and EGFR mutations were detected in higher proportions by alternative highly sensitive molecular techniques compared with direct Sanger sequencing. However, minor KRAS-mutated subclones offered no prognostic value when representing less than 1% of the tumor cells.
为了评估表皮生长因子受体（EGFR）突变状态在非小细胞肺癌（NSCLC）患者中接受 EGFR-TKI 治疗的效果，进行了一项前瞻性研究。这项研究旨在验证 EGFR/KRAS 突变在接受第一代酪氨酸激酶抑制剂厄洛替尼治疗的晚期 NSCLC 患者中的预后价值。ERMETIC2 是一项辅助项目，使用高度敏感的分子检测方法评估常见 EGFR/KRAS 突变亚克隆对预后的临床价值。
对 228 例 NSCLC 患者（59%为腺癌，37%为女性，19%为从不吸烟/曾经吸烟）的肿瘤样本进行了重新分析，使用了替代的高度敏感的分子技术。采用多变量 Cox 模型进行预后分析。
使用替代的高度敏感技术，新发现了 16 个 EGFR 和 51 个 KRAS 补充突变，均为独特突变，总体发生率分别为 12.3%（n=28）和 33.3%（n=76）。使用实时聚合酶链反应（杂交探针），这些突变与无进展生存期（P=0.02）和总生存期（OS）（P=0.01）显著相关，EGFR 突变患者的无进展生存期（风险比 [HR]，0.46；95%置信区间 [CI]，0.28-0.78）和 OS（HR，0.56；95%CI，0.31-1）更好，KRAS 突变和 OS 更差（HR，1.63；95%CI，1.09-2.44）。使用最敏感的技术检测 KRAS 夹聚合酶链反应-KRAS 突变亚克隆对 OS 没有影响。
与直接 Sanger 测序相比，替代的高度敏感分子技术检测到更高比例的 KRAS 和 EGFR 突变。然而，当 KRAS 突变亚克隆代表肿瘤细胞的比例小于 1%时，它们并没有提供预后价值。
Zotero 插件