Monitoring of somatic mutations in circulating cell-free DNA by digital PCR and next-generation sequencing during afatinib treatment in patients with lung adenocarcinoma positive for EGFR activating mutations
Monitoring of somatic mutations in circulating cell-free DNA by digital PCR and next-generation sequencing during afatinib treatment in patients with lung adenocarcinoma positive for EGFR activating mutations
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DOI：
10.1093/annonc/mdw531
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发表时间：
2017-01-01
影响因子：
50.5
通讯作者：
Okamoto, I.
中科院分区：
文献类型：
--
作者：
Iwama, E.;Sakai, K.;Okamoto, I.
背景：循环无细胞DNA（cfDNA）分析正在深入研究其识别肿瘤体细胞突变的潜力。我们现在已经探索了在表皮生长因子受体（EGFR）抑制剂阿法替尼治疗患者期间使用数字聚合酶链反应（dPCR）和下一代测序（NGS）进行液体活检检测的有用性。患者和方法：符合条件的患者患有晚期肺腺癌，伴有EGFR激活突变，并接受阿法替尼治疗。在阿法替尼治疗前和治疗期间（4周和24周）以及疾病进展时采集血浆样本。采用dPCR和NGS技术分析肿瘤和血浆DNA。客观缓解率和中位无进展生存期（PFS）分别为77.1%和13.8个月。32例患者的肿瘤和血浆DNA可用。dPCR和NGS分别在81.3%和71.9%的基线cfDNA样本中检测到EGFR激活突变。在19例接受阿法替尼治疗24周的患者中，dPCR检测cfDNA中EGFR突变等位基因的数量在治疗开始后迅速显著下降，无法检测或仅在低拷贝数时可检测到（
Background: Analysis of circulating cell-free DNA (cfDNA) is under intensive investigation for its potential to identify tumor somatic mutations. We have now explored the usefulness of such liquid biopsy testing with both the digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS) during treatment of patients with the epidermal growth factor receptor (EGFR) inhibitor afatinib.Patients and methods: Eligible patients had advanced lung adenocarcinoma with EGFR activating mutations and were treated with afatinib. Plasma samples were collected before and during (4 and 24 weeks) afatinib treatment as well as at disease progression. Tumor and plasma DNA were analyzed by dPCR and NGS.Results: Thirty-five patients were enrolled. The objective response rate and median progression-free survival (PFS) were 77.1% and 13.8 months, respectively. Tumor and plasma DNA were available for 32 patients. dPCR and NGS detected EGFR activating mutations in 81.3% and 71.9% of baseline cfDNA samples, respectively. In 19 patients treated with afatinib for similar to 24 weeks, the number of EGFR mutant alleles detected in cfDNA by dPCR declined rapidly and markedly after treatment onset, becoming undetectable or detectable at only a low copy number (