Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686).
Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686).
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DOI：
10.1158/1078-0432.ccr-15-1260
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发表时间：
2016-05-15
期刊：
影响因子：
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通讯作者：
Wakelee H
中科院分区：
文献类型：
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作者：
Karlovich C;Goldman JW;Sun JM;Mann E;Sequist LV;Konopa K;Wen W;Angenendt P;Horn L;Spigel D;Soria JC;Solomon B;Camidge DR;Gadgeel S;Paweletz C;Wu L;Chien S;O'Donnell P;Matheny S;Despain D;Rolfe L;Raponi M;Allen AR;Park K;Wakelee H
尚未广泛探索NSCLC患者EGFR耐药突变T790 M的血浆检测评价。我们研究了匹配的肿瘤组织和血浆中EGFR激活和T790 M突变的检测，主要来自对第一代EGFR抑制剂获得性耐药的患者。样本来自两项研究，一项是观察性研究，另一项是rociletinib的I期试验，rociletinib是一种EGFR的多药选择性抑制剂，靶向激活突变和T790 M。用cobas EGFR血浆检测和BEAMing进行血浆检测。cobas血浆和肿瘤结果之间的阳性百分比一致性（PPA）对于激活突变为73%（55/75），对于T790 M为64%（21/33）。BEAMing血浆和肿瘤结果之间的PPA对于激活突变为82%（49/60），对于T790 M为73%（33/45）。发现胸外（M1 b）与胸内（M1 a/M0）疾病的存在与识别血浆中EGFR突变的能力密切相关（P < 0.001）。对于Cobas肿瘤T790 M阳性患者，Rociletinib客观缓解率（ORR）为52% [95%置信区间（CI），31 - 74%]，对于BEAMing血浆T790 M阳性患者，ORR为44%（95% CI，25 - 63%）。在8例记录部分缓解的患者中，7例在治疗第21天观察到血浆突变型EGFR水平降至≤10分子/mL。这些结果表明，cobas和BEAMing血浆检测可以作为非侵入性评估和监测NSCLC中T790 M耐药突变的有用工具，并可以通过识别由于肿瘤异质性或活检不足而遗漏的T790 M突变来补充肿瘤检测。
The evaluation of plasma testing for the EGFR resistance mutation T790M in NSCLC patients has not been broadly explored. We investigated the detection of EGFR activating and T790M mutations in matched tumor tissue and plasma, mostly from patients with acquired resistance to first-generation EGFR inhibitors. Samples were obtained from two studies, an observational study and a phase I trial of rociletinib, a mutant-selective inhibitor of EGFR that targets both activating mutations and T790M. Plasma testing was performed with the cobas EGFR plasma test and BEAMing. The positive percent agreement (PPA) between cobas plasma and tumor results was 73% (55/75) for activating mutations and 64% (21/33) for T790M. The PPA between BEAMing plasma and tumor results was 82% (49/60) for activating mutations and 73% (33/45) for T790M. Presence of extrathoracic (M1b) versus intrathoracic (M1a/M0) disease was found to be strongly associated with ability to identify EGFR mutations in plasma (P < 0.001). Rociletinib objective response rates (ORR) were 52% [95% confidence interval (CI), 31 – 74%] for cobas tumor T790M-positive and 44% (95% CI, 25 – 63%) for BEAMing plasma T790M-positive patients. A drop in plasma-mutant EGFR levels to ≤10 molecules/mL was seen by day 21 of treatment in 7 of 8 patients with documented partial response. These findings suggest the cobas and BEAMing plasma tests can be useful tools for noninvasive assessment and monitoring of the T790M resistance mutation in NSCLC, and could complement tumor testing by identifying T790M mutations missed because of tumor heterogeneity or biopsy inadequacy.