动态血浆 EGFR 突变状态可预测 EGFR 突变型肺腺癌患者的 EGFR-TKI 疗效。

Dynamic plasma EGFR mutation status as a predictor of EGFR-TKI efficacy in patients with EGFR-mutant lung adenocarcinoma.

机构信息

*Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, ROC; †Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; ‡Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; §Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; ‖Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan, ROC; ¶Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; #Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, ROC; **Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; ††Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; ‡‡Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; §§Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC; ‖‖Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan, ROC; and ¶¶Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.

出版信息

J Thorac Oncol. 2015 Apr;10(4):603-10. doi: 10.1097/JTO.0000000000000443.

DOI:10.1097/JTO.0000000000000443

PMID:25514801

Abstract

BACKGROUND

Epidermal growth factor receptor (EGFR) mutation status in lung cancer can effectively predict EGFR-tyrosine kinase inhibitor (TKI) efficacy. We evaluated the role of dynamic plasma cell-free DNA EGFR mutation status in outcome prediction.

METHODS

Advanced lung adenocarcinoma patients were enrolled and prospectively observed for outcomes of EGFR-TKI treatment. Peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method was developed to assess EGFR mutations in matched tumor and serial plasma cell-free DNA specimens.

RESULTS

A total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R). Pretreatment plasma used for EGFR mutation testing showed a sensitivity of 59.7% and a specificity of 100%. Detection sensitivity was significantly higher in stage IV-M1b patients compared with stage IIIb and IV-M1a patients (78.0% versus 23.8%, p < 0.001). All patients who presented with EGFR-mutant tumors received first-line EGFR-TKI therapy. The objective response rate and disease control rate were 74.2% and 82.3%, respectively. Median progression-free survival and overall survival were 8.8 months (95% CI: 6.6-11.0) and 20.5 months (95% CI 15.1-26.0), respectively. Failure to clear plasma EGFR mutations after EGFR-TKI treatment was an independent predictor of lower disease control rate (odds ratio 5.26 [95% CI: 1.13-24.44]; p = 0.034), shorter progression-free survival (hazard ratio: 1.97 [95% CI: 1.33-2.91]; p = 0.001), and shorter overall survival (hazard ratio: 1.82 [95% CI: 1.04-3.18], p = 0.036).

CONCLUSION

Changes in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor.

摘要

背景

表皮生长因子受体（EGFR）突变状态可有效预测肺癌患者接受 EGFR 酪氨酸激酶抑制剂（TKI）治疗的效果。本研究旨在评估动态血浆游离 DNA（cfDNA）EGFR 突变状态在预测结局方面的作用。

方法

前瞻性纳入晚期肺腺癌患者，观察其接受 EGFR-TKI 治疗的结局。采用肽核酸-拉链核酸聚合酶链反应夹心法检测配对肿瘤组织和连续血浆 cfDNA 标本中的 EGFR 突变。

结果

共纳入 72 例患者，其中 62 例（86.1%）患者存在 EGFR 突变型肿瘤（34 例存在外显子 19 缺失，28 例存在 L858R 突变）。用于 EGFR 突变检测的血浆标本检测敏感性为 59.7%，特异性为 100%。IV-M1b 期患者的检测敏感性显著高于 IIIb 期和 IV-M1a 期患者（78.0%比 23.8%，p<0.001）。所有 EGFR 突变型肿瘤患者均接受了一线 EGFR-TKI 治疗。客观缓解率和疾病控制率分别为 74.2%和 82.3%。中位无进展生存期和总生存期分别为 8.8 个月（95%CI：6.6-11.0）和 20.5 个月（95%CI：15.1-26.0）。EGFR-TKI 治疗后血浆 EGFR 突变未清除是疾病控制率较低的独立预测因素（比值比 5.26[95%CI：1.13-24.44]；p=0.034）、无进展生存期较短（风险比：1.97[95%CI：1.33-2.91]；p=0.001）和总生存期较短（风险比：1.82[95%CI：1.04-3.18]；p=0.036）。