Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical Center of Vienna, Vienna, Austria.
Department of Respiratory and Critical Care Medicine, and Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria.
J Thorac Oncol. 2018 Jun;13(6):821-830. doi: 10.1016/j.jtho.2018.02.014. Epub 2018 Mar 2.
Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine.
From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients.
T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers.
Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.
奥希替尼是经表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗后进展的表皮生长因子受体 T790M 突变型非小细胞肺癌患者的标准治疗方法。我们研究了游离血浆 DNA 中的 T790M 检测是否可用于临床常规选择奥希替尼治疗的患者。
2015 年 4 月至 2016 年 11 月，我们纳入了 119 例接受 EGFR-TKI 治疗后进展的晚期 EGFR 突变型非小细胞肺癌患者。所有患者均采用液滴数字聚合酶链反应检测游离血浆 DNA 中的 T790M 突变状态，并在部分患者中进行组织分析。
通过游离血浆 DNA 分析，85 例（93%）患者和 6 例（7%）血浆阴性患者检测到 T790M 突变，通过肿瘤再活检。91 例 T790M 阳性患者中有 89 例接受奥希替尼治疗。中位无进展生存期（PFS）为 10.1 个月（95%置信区间：8.1-12.1）。中位生存期未达到，1 年生存率为 64%。在 T790M 阳性患者（n=91）的意向治疗人群中，总缓解率为 70%。与 T790M 拷贝数低（<10 拷贝/mL）的患者相比，T790M 拷贝数高（≥10 拷贝/mL）的患者 PFS 趋势更短（PFS 的风险比为 1.72，95%置信区间：0.92-3.2，p=0.09）。总体生存情况也观察到类似的趋势（总生存的风险比为 2.16，95%置信区间：0.89-5.25，p=0.09）。基于 T790M 拷贝数，反应率无差异。
使用数字聚合酶链反应的血浆基因分型对选择接受奥希替尼治疗的一线 EGFR-TKI 治疗后进展的患者具有临床意义。
