AstraZeneca, Alderley Park, United Kingdom.
National Taiwan University Hospital, Taipei, Republic of China.
J Thorac Oncol. 2017 Jul;12(7):1061-1070. doi: 10.1016/j.jtho.2017.04.003. Epub 2017 Apr 17.
Tumor biopsies for detecting EGFR mutations in advanced NSCLC are invasive, costly, and not always feasible for patients with late-stage disease. The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease progression after previous EGFR tyrosine kinase inhibitor therapy was investigated to determine eligibility for osimertinib treatment.
Matched tumor tissue and plasma samples from patients screened for the AURA extension and AURA2 phase II studies were tested for EGFR mutations by using tissue- and plasma-based cobas EGFR mutation tests. Plasma test performance was assessed by using the cobas tissue test and a next-generation sequencing method (MiSeq [Illumina Inc., San Diego, CA]) as references. The objective response rate, measured by blinded independent central review, was assessed in patients receiving osimertinib with a plasma T790M mutation-positive status.
During screening, 551 patients provided matched tumor tissue and plasma samples. Pooled analysis of the positive and negative percent agreements between the cobas plasma and tissue tests for detection of T790M mutation were 61% and 79%, respectively. Comparing cobas plasma test with next-generation sequencing demonstrated positive and negative percent agreements of 90% or higher. The objective response rate was 64% (95% confidence interval: 57-70) in T790M mutation-positive patients by both cobas tissue and plasma tests (evaluable for response).
The cobas plasma test detected the T790M mutation in 61% of tumor tissue T790M mutation-positive patients. To mitigate the risk of false-negative plasma results, patients with a negative plasma result should undergo a tissue test where feasible.
晚期 NSCLC 患者的肿瘤活检用于检测 EGFR 突变具有侵袭性、费用高，并且并非对所有晚期疾病患者都可行。本研究旨在调查在先前接受 EGFR 酪氨酸激酶抑制剂（TKI）治疗后疾病进展的 NSCLC 患者中，使用 cobas EGFR Mutation Test v2（罗氏分子系统公司，加利福尼亚州普莱森顿）检测血浆样本 EGFR 突变的临床应用价值，以确定奥希替尼治疗的资格。
筛选参加 AURA 扩展和 AURA2 二期研究的患者，用组织和血浆 cobas EGFR 突变检测试剂盒检测配对的肿瘤组织和血浆样本中的 EGFR 突变。以 cobas 组织检测和下一代测序方法（MiSeq[Illumina 公司，圣地亚哥，加利福尼亚州]）为参考，评估血浆检测的性能。在接受奥希替尼治疗且血浆 T790M 突变阳性的患者中评估客观缓解率，由盲法独立中心审查进行评估。
筛选期间，551 例患者提供了配对的肿瘤组织和血浆样本。cobas 血浆和组织检测对 T790M 突变检测的阳性和阴性百分比一致率分别为 61%和 79%。与下一代测序比较，cobas 血浆检测的阳性和阴性百分比一致率为 90%或更高。T790M 突变阳性患者（可评估反应），cobas 组织和血浆检测均为阳性的患者客观缓解率为 64%（95%置信区间：57%-70%）。
cobas 血浆检测在 61%的肿瘤组织 T790M 突变阳性患者中检测到 T790M 突变。为了降低假阴性血浆结果的风险，对于血浆结果阴性的患者，应在可行的情况下进行组织检测。
