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首页> 外文期刊>Journal of Thoracic Disease >Standard dose osimertinib for erlotinib refractory T790M-negative EGFR -mutant non-small cell lung cancer with leptomeningeal disease
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Standard dose osimertinib for erlotinib refractory T790M-negative EGFR -mutant non-small cell lung cancer with leptomeningeal disease

机译：厄洛替尼难治性T790M阴性EGFR突变型非小细胞肺癌伴软脑膜病的标准剂量奥西替尼

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Background: Leptomeningeal spread in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR ) mutations who experience disease progression on TKIs portends a poor prognosis. Mutation profiling of tumour DNA in cerebrospinal fluid (CSF) samples can be used to determine the presence of the EGFR T790M resistance mutation, indicating that osimertinib, a CNS-penetrating 3 rd generation TKI may be efficacious. Methods: Eight patients on EGFR TKIs who progressed with cytology-proven leptomeningeal disease at our institution were studied. EGFR mutations were profiled in CSF using droplet digital PCR (ddPCR) and compared to matched plasma samples. Clinical characteristics and survival outcomes on subsequent therapies tailored to ddPCR analysis were reported. Results: None of the four patients who developed leptomeningeal disease while receiving 1st generation EGFR TKIs developed the EGFR T790M mutation in CSF. One patient who did not have extra-cranial disease and was EGFR T790M-negative in both plasma and CSF was nevertheless treated with standard-dose osimertinib, and achieved a rapid and durable response lasting 9 months to date. Three patients developed leptomeningeal disease on osimertinib, with one patient developing the EGFR C797S mutation in a cis-allelic conformation with the EGFR T790M mutation in plasma. Conclusions: Standard-dose osimertinib resulted in a clinically meaningful response in a patient with EGFR T790M-negative 1st generation EGFR TKI refractory leptomeningeal disease. Next generation sequencing and ddPCR has a role at identifying the C797S mutation and its allelic conformation with the T790M mutation with clinical implications.
机译：背景：在表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者中，脑膜上皮细胞的扩散在TKIs上经历疾病进展预示不良预后。脑脊液（CSF）样品中肿瘤DNA的突变图谱可用于确定EGFR T790M抗药性突变的存在，这表明渗透性CNS的第三代TKI奥西替尼可能是有效的。方法：对我院八例EGFR TKIs进展为细胞学证实的肾小球脑膜病的患者进行研究。使用液滴数字PCR（ddPCR）在CSF中分析EGFR突变，并与匹配的血浆样品进行比较。报告了针对ddPCR分析的后续疗法的临床特征和生存结果。结果：在接受第一代EGFR TKI的同时发生了软脑膜疾病的四名患者中，没有一例在CSF中发生EGFR T790M突变。一名没有颅外疾病且血浆和CSF均为EGFR T790M阴性的患者仍接受标准剂量的奥西替尼治疗，迄今已持续9个月，获得了快速而持久的反应。 3例患者在osimertinib上患了软脑膜病，其中1例患者的EGFR C797S突变呈等位基因构象，血浆中有EGFR T790M突变。结论：标准剂量的奥西替尼在EGFR T790M阴性的第一代EGFR TKI难治性软脑膜病患者中产生了临床上有意义的反应。下一代测序和ddPCR在鉴定C797S突变及其与T790M突变的等位基因构象方面具有作用，具有临床意义。

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