Clinical Validation of a PCR Assay for the Detection of EGFR Mutations in Non-Small-Cell Lung Cancer: Retrospective Testing of Specimens from the EURTAC Trial
Clinical Validation of a PCR Assay for the Detection of EGFR Mutations in Non-Small-Cell Lung Cancer: Retrospective Testing of Specimens from the EURTAC Trial
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DOI：
10.1371/journal.pone.0089518
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发表时间：
2014-02-25
期刊：
影响因子：
3.7
通讯作者：
Taron, Miquel
中科院分区：
文献类型：
--
作者：
Benlloch, Susana;Luisa Botero, Maria;Taron, Miquel
EURTAC试验表明，酪氨酸激酶抑制剂（TKI）厄洛替尼（erlotinib）作为治疗晚期非小细胞肺癌（NSCLC）的一线治疗方法优于化疗，这些NSCLC主要是在高加索人群中携带EGFR激活突变。基于EURTAC和几个亚洲试验，抗EGFR TKIs是EGFR突变阳性NSCLC的标准治疗。我们试图验证一种快速的多重EGFR突变检测作为辅助诊断检测来选择接受这种治疗的患者。使用实验室开发的测试（LDTs）组合对EURTAC试验样本进行了EGFR突变的前瞻性筛选，并使用cobas EGFR突变测试（EGFR PCR测试）进行了回顾性测试。EGFR PCR检测结果与原始LDT结果和Sanger测序结果进行了比较，使用了试验筛选的患者标本子集。在接受试验筛选的1044例患者中，有487例（47%）存在残留组织。EGFR PCR检测显示与LDT结果高度一致，总体一致性为96.3%。EGFR PCR检测到EGFR突变的患者的临床结果与整个EURTAC队列非常相似。EGFR PCR检测与Sanger测序的一致性为90.6%。在78.9%的不一致样本中，EGFR PCR检测结果被敏感的深度测序试验证实。这项回顾性研究证明了EGFR PCR检测在准确选择抗EGFR TKI治疗患者中的临床应用。相对于Sanger测序，EGFR PCR测试表现出更好的性能。
The EURTAC trial demonstrated that the tyrosine kinase inhibitor (TKI) erlotinib was superior to chemotherapy as first-line therapy for advanced non-small cell lung cancers (NSCLC) that harbor EGFR activating mutations in a predominantly Caucasian population. Based on EURTAC and several Asian trials, anti-EGFR TKIs are standard of care for EGFR mutation-positive NSCLC. We sought to validate a rapid multiplex EGFR mutation assay as a companion diagnostic assay to select patients for this therapy. Samples from the EURTAC trial were prospectively screened for EGFR mutations using a combination of laboratory-developed tests (LDTs), and tested retrospectively with the cobas EGFR mutation test (EGFR PCR test). The EGFR PCR test results were compared to the original LDT results and to Sanger sequencing, using a subset of specimens from patients screened for the trial. Residual tissue was available from 487 (47%) of the 1044 patients screened for the trial. The EGFR PCR test showed high concordance with LDT results with a 96.3% overall agreement. The clinical outcome of patients who were EGFR-mutation detected by the EGFR PCR test was very similar to the entire EURTAC cohort. The concordance between the EGFR PCR test and Sanger sequencing was 90.6%. In 78.9% of the discordant samples, the EGFR PCR test result was confirmed by a sensitive deep sequencing assay. This retrospective study demonstrates the clinical utility of the EGFR PCR test in the accurate selection of patients for anti-EGFR TKI therapy. The EGFR PCR test demonstrated improved performance relative to Sanger sequencing.