携带有 EGFR 突变的非小细胞肺癌（NSCLC）的临床和分子特征：全国性法国胸科协作组（IFCT）计划的结果。
Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program.
机构信息
Department of Chest, Centre Hospitalier Universitaire de Strasbourg, Nouvel Hôpital Civil, Strasbourg.
Department of Biology and Pathology, Centre Hospitalier Universitaire de Bordeaux, Pessac;; Histology and Molecular Pathology of Tumors, Université de Bordeaux, Bordeaux.
出版信息
Ann Oncol. 2017 Nov 1;28(11):2715-2724. doi: 10.1093/annonc/mdx404.
BACKGROUND
EGFR mutations cause inconsistent response to EGFR tyrosine-kinase inhibitors (TKI). To better understand these features, we reviewed all cases of EGFR-mutated non-small-cell lung cancer collected in the Biomarkers France database.
PATIENTS AND METHODS
Of 17 664 patients, 1837 (11%) with EGFR-mutated non-small-cell lung cancer were retrospectively analyzed for clinical and molecular characteristics. Results were correlated with survival and treatment response for the 848 stage IV patients.
RESULTS
EGFR exon 18, 19, 20 and 21 mutations were found in 102 (5.5%), 931 (51%), 102 (5.5%) and 702 (38%) patients, respectively. Over 50% of exon 18 and 20 mutated patients were smokers. The median follow-up was 51.7 months. EGFR mutation type was prognostic of overall survival (OS) versus wild-type {exon 19: hazard ratio (HR)=0.51 [95% confidence interval (CI): 0.41-0.64], P < 0.0001; exon 21: HR = 0.76 (95% CI: 0.61-0.95), P = 0.002; exon 20: HR = 1.56 (95% CI: 1.02-2.38), P = 0.004}. EGFR mutation type was prognostic of progression-free survival versus wild-type [exon 19: HR = 0.62 (95% CI: 0.49-0.78), P < 0.0001; exon 20: HR = 1.46 (95% CI: 0.96-2.21), P = 0.07]. First-line treatment choice did not influence OS in multivariate analysis. First-line TKI predicted improved progression-free survival versus chemotherapy [HR = 0.67 (95% CI: 0.53-0.85), P = 0.001]. OS was longer for del19 versus L858R, which was associated with better OS compared with other exon 21 mutations, including L861Q. TKI improved survival in patients with exon 18 mutations, while chemotherapy was more beneficial for exon 20-mutated patients.
CONCLUSION
EGFR mutation type can inform the most appropriate treatment. Therapeutic schedule had no impact on OS in our study, although TKI should be prescribed in first-line considering the risk of missing the opportunity to use this treatment.
背景
EGFR 突变导致 EGFR 酪氨酸激酶抑制剂（TKI）的反应不一致。为了更好地了解这些特征，我们回顾了 Biomarkers France 数据库中收集的所有 EGFR 突变型非小细胞肺癌病例。
患者和方法
在 17664 名患者中，对 1837 名（11%）EGFR 突变型非小细胞肺癌患者进行了回顾性分析，以评估其临床和分子特征。对 848 名 IV 期患者的治疗结果与生存情况进行了相关性分析。
结果
发现 EGFR 外显子 18、19、20 和 21 突变分别存在于 102 例（5.5%）、931 例（51%）、102 例（5.5%）和 702 例（38%）患者中。超过 50%的外显子 18 和 20 突变患者为吸烟者。中位随访时间为 51.7 个月。EGFR 突变类型与野生型患者的总生存期（OS）有关{外显子 19：风险比（HR）=0.51[95%置信区间（CI）：0.41-0.64]，P<0.0001；外显子 21：HR=0.76（95%CI：0.61-0.95），P=0.002；外显子 20：HR=1.56（95%CI：1.02-2.38），P=0.004}。EGFR 突变类型与野生型患者的无进展生存期（PFS）有关{外显子 19：HR=0.62（95%CI：0.49-0.78），P<0.0001；外显子 20：HR=1.46（95%CI：0.96-2.21），P=0.07}。多因素分析显示，一线治疗选择不影响 OS。一线 TKI 预测与化疗相比，可改善 PFS{HR=0.67（95%CI：0.53-0.85），P=0.001}。与其他外显子 21 突变（包括 L861Q）相比，del19 与 L858R 相比，OS 更长。TKI 改善了外显子 18 突变患者的生存，而化疗对外显子 20 突变患者更有益。
结论
EGFR 突变类型可提供最佳治疗方案。在我们的研究中，治疗方案对 OS 没有影响，尽管考虑到错过使用这种治疗机会的风险，TKI 应该作为一线治疗药物。
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