Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

中文翻译：

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无细胞血浆 DNA 指导的奥希替尼治疗晚期 EGFR 突变的 NSCLC 患者

简介：奥希替尼是已接受 EGFR-酪氨酸激酶抑制剂（TKI）预处理的晚期 EGFR T790M 突变非小细胞肺癌患者的标准治疗方法。我们研究了用于 T790M 检测的无细胞血浆 DNA 是否可用于选择临床常规中接受奥希替尼治疗的患者。方法：从 2015 年 4 月到 2016 年 11 月，我们纳入了 119 名在 EGFR-TKI 治疗下进展的晚期 EGFR 突变非小细胞肺癌患者。通过所有患者的液滴数字聚合酶链反应和选定患者的组织分析，在无细胞血浆 DNA 中评估了 T790M 突变状态。结果：通过游离血浆 DNA 分析在 85 名 (93%) 患者中检测到 T790M 突变，通过肿瘤再活检在 6 名 (7%) 血浆阴性患者中检测到 T790M 突变。91 名 T790M 阳性患者中有 89 名接受了奥希替尼治疗。中位无进展生存期 (PFS) 为 10.1 个月（95% 置信区间 [CI]：8.1-12.1）。未达到中位生存率，1 年生存率为 64%。在意向治疗人群中，T790M 阳性患者（n = 91）的缓解率为 70%。与低 T790M 拷贝数（<10 拷贝/mL）的患者相比，具有高 T790M 拷贝数（≥10 拷贝/mL）的患者的 PFS 趋于更短（PFS 的风险比 = 1.72，95% CI：0.92–3.2， p = 0.09）。总体生存率观察到了类似的趋势（总体生存率的风险比 = 2.16，95% CI：0.89–5.25，p = 0.09）。基于 T790M 拷贝数，没有观察到响应率的差异。结论：