Clearing of circulating tumour DNA predicts clinical response to osimertinib in EGFR mutated lung cancer patients
Clearing of circulating tumour DNA predicts clinical response to osimertinib in EGFR mutated lung cancer patients
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DOI：
10.1016/j.lungcan.2020.03.020
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发表时间：
2020-05-01
期刊：
影响因子：
5.3
通讯作者：
Meldgaard, Peter
中科院分区：
文献类型：
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作者：
Ebert, Eva Boysen Fynboe;McCulloch, Tine;Meldgaard, Peter
目的：酪氨酸激酶抑制剂（TKI）是表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）患者的一线治疗选择。然而，患者的反应各不相同，因此需要良好的生物标志物预测更好的反应。EGFR突变在患者血液中检测为循环肿瘤DNA（ctDNA）。研究表明，一线TKI治疗期间清除ctDNA可预测第一代和第二代TKI治疗的结局。我们的目的是调查ctDNA清除在后续的治疗线与第三代TKI osimertinib治疗的结果措施的影响：在总共225例患者被纳入一个前瞻性的，多中心的研究，其中连续的血液样本进行监测EGFR突变在全身治疗线，使用Cobas（R）EGFR突变测试V2。本研究关注82例接受奥希替尼全身预治疗患者ctDNA中的EGFR突变，结果：奥希替尼治疗后清除血液中所有EGFR突变，显著预测无进展生存率、客观缓解率和疾病控制率。70%的患者在ctDNA中发现原发性致敏EGFR突变，近三分之二的病例伴有T790M突变。在所有病例中T790M突变均被清除，而伴随的致敏突变不一定被清除。然而，T790M清除而不同时清除原发致敏突变并不能预测临床反应。无论是奥希替尼治疗前T790 M的检测，也不是EGFR突变的存在下，在奥希替尼开始预测clinical outcomes.Conclusion：清除后奥希替尼治疗开始在晚期NSCLC患者的ctDNA中的EGFR突变是有用的作为一个积极的预测临床结果。
Objectives: Tyrosine kinase inhibitors (TKIs) are first line treatment choices for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). However, responses vary among patients, therefore good biomarkers predicting better responses are required. EGFR mutations are detected in the blood from patients as circulating tumour DNA (ctDNA). Studies have shown that clearing ctDNA during first line TKI treatment predicts outcomes for first and second generation TKI treatments. We aimed to investigate the effects on outcome measures of ctDNA clearing in subsequent treatment lines to treatment with the third generation TKI osimertinib.Methods: In total, 225 patients were included in a prospective, multicentre study, where consecutive blood samples were monitored for EGFR mutations during systemic treatment lines, using the Cobas (R) EGFR mutation test v2. This study focused on EGFR mutations in ctDNA of 82 systemically pre-treated patients receiving osimertinib.Results: Clearing all EGFR mutations from the blood after osimertinib treatment, significantly predicted progression-free survival, objective response rates and disease control rates. Primary sensitising EGFR mutations were found in ctDNA in 70 % of patients, and were accompanied by the T790M mutation in nearly two thirds of cases. The T790M mutation was cleared in all cases, while the accompanying sensitising mutations did not necessarily clear. However, T790M clearing without simultaneously clearing of the primary sensitising mutation did not predict clinical responses. Neither the detection of T790M before osimertinib treatment, nor the presence of EGFR mutations at the time of osimertinib initiation predicted clinical outcomes.Conclusion: The clearing of EGFR mutations in ctDNA after osimertinib treatment initiation in patients with advanced NSCLC is useful as a positive predictor of clinical outcome.