Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy
Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy
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DOI：
10.1158/1078-0432.ccr-14-2594
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发表时间：
2015-07-15
影响因子：
11.5
通讯作者：
Wu, Lin
中科院分区：
文献类型：
--
作者：
Mok, Tony;Wu, Yi-Long;Wu, Lin
目的：基于血液的无循环（cf）肿瘤DNA可能是NSCLC中基于组织的EGFR突变检测的替代方法。这种探索性分析比较匹配的肿瘤和血液样本FASTACT-2 study.Experimental Design：患者随机接受6个周期的吉西他滨/铂加序贯厄洛替尼或安慰剂。使用cobas组织检测和cobas血液检测（开发中）进行EGFR突变检测。在基线、第3周期和进展时的血液样本评估血液检测检出率、灵敏度和特异性;与匹配的肿瘤分析（n = 238）的一致性，以及与无进展生存期（PFS）和总生存期（OS）的相关性。对于基线EGFR mut（+）cfDNA的患者，厄洛替尼和安慰剂的中位PFS分别为13.1个月和6.0个月[HR，0.22; 95%置信区间（CI），0.14-0.33，P < 0.0001]，EGFR mut（-）cfDNA亚组分别为6.2个月和6.1个月（HR，0.83; 95% CI，0.65-1.04，P = 0.1076）。对于基线EGFR mut（+）cfDNA患者，第3周期EGFR mut（+）cfDNA与第3周期EGFR mut（-）患者的中位PFS分别为7.2个月与12.0个月（HR，0.32; 95%CI，0.21-0.48，P < 0.0001）;按周期3状态列出的中位OS分别为18.2和31.9个月（HR，0.51; 95%CI，0.31-0.84，P = 0.0066）。结论：基于血液的EGFR突变检测具有较高的敏感性和特异性。cfDNA EGFR突变状态相对于基线的动态变化可预测临床结局。(C)2015年AACR。
Purpose: Blood-based circulating-free (cf) tumor DNA may be an alternative to tissue-based EGFR mutation testing in NSCLC. This exploratory analysis compares matched tumor and blood samples from the FASTACT-2 study.Experimental Design: Patients were randomized to receive six cycles of gemcitabine/platinum plus sequential erlotinib or placebo. EGFR mutation testing was performed using the cobas tissue test and the cobas blood test (in development). Blood samples at baseline, cycle 3, and progression were assessed for blood test detection rate, sensitivity, and specificity; concordance with matched tumor analysis (n = 238), and correlation with progression-free survival (PFS) and overall survival (OS).Results: Concordance between tissue and blood tests was 88%, with blood test sensitivity of 75% and a specificity of 96%. Median PFS was 13.1 versus 6.0 months for erlotinib and placebo, respectively, for those with baseline EGFR mut(+) cfDNA [HR, 0.22; 95% confidence intervals (CI), 0.14-0.33, P < 0.0001] and 6.2 versus 6.1 months, respectively, for the EGFR mut(-) cfDNA subgroup (HR, 0.83; 95% CI, 0.65-1.04, P = 0.1076). For patients with EGFR mut(+) cfDNA at baseline, median PFS was 7.2 versus 12.0 months for cycle 3 EGFR mut(+) cfDNA versus cycle 3 EGFR mut(-) patients, respectively (HR, 0.32; 95% CI, 0.21-0.48, P < 0.0001); median OS by cycle 3 status was 18.2 and 31.9 months, respectively (HR, 0.51; 95% CI, 0.31-0.84, P = 0.0066). Conclusions: Blood-based EGFR mutation analysis is relatively sensitive and highly specific. Dynamic changes in cfDNA EGFR mutation status relative to baseline may predict clinical outcomes. (C) 2015 AACR.