High ratio of T790M to EGFR activating mutations correlate with the osimertinib response in non-small-cell lung cancer
High ratio of T790M to EGFR activating mutations correlate with the osimertinib response in non-small-cell lung cancer
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DOI：
10.1016/j.lungcan.2017.12.018
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发表时间：
2018-03-01
期刊：
影响因子：
5.3
通讯作者：
Katayama, Ryohei
中科院分区：
文献类型：
--
作者：
Ariyasu, Ryo;Nishikawa, Shingo;Katayama, Ryohei
目的：奥西替尼是一种第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，可以克服Thr790Met （T790M）突变引起的耐药性。然而，奥西替尼偶尔在一小部分患者中显示出有限的疗效。我们研究了T790M与EGFR激活突变的比例与对奥西替尼的反应之间的相关性。材料与方法：2016年4月至2017年4月，44例患者在日本癌症研究基金会癌症研究所医院开始奥希替尼治疗。我们使用液滴数字PCR对33例患者的细胞学样本进行了EGFR突变分析。我们计算了T790M与EGFR激活突变的比率，并将其与对奥希替尼的全身反应相关联。结果：在33例患者的肿瘤中，T790M与EGFR激活突变的平均比值为0.420。33例患者中有21例肿瘤T790M比值>= 0.4。T790M比值为>= 0.4的患者的奥西替尼缓解率（92.3%）显著高于T790M比值< 0.4的患者（52.6%,p = 0.0237）。我们检验了T790M比值与肿瘤切除率的相关性，得到r = 0.417 （p = 0.0175）的系数。T790M比值为>= 0.4的患者，中位无进展生存期为355天，比T790M比值< 0.4的患者（中位264天）更长，但不显著。T790M比值为>= 0.4的患者，从一线治疗开始的中位治疗时间为931天，显著长于T790M比值< 0.4的患者（中位567.5天）（p = 0.044）。结论：肿瘤中T790M与EGFR激活突变的比值可能与奥西替尼的疗效相关，且T790M比值较高的患者治疗史较长。
Objectives: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that can overcome resistance due to the Thr790Met (T790M) mutation. However, osimertinib occasionally shows limited efficacy in a small population of patients. We investigated the correlation between the ratio of T790M to EGFR activating mutation and the response to osimertinib.Materials and methods: Between April 2016 and April 2017, 44 patients started osimertinib therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. We performed EGFR mutation analysis of cytological samples from 33 patients using droplet digital PCR. We calculated the ratio of T790M to EGFR activating mutations and correlated it with the systemic response to osimertinib.Results: In tumors from the 33 patients, the average ratio of T790M to EGFR activating mutations was 0.420. Twenty-one of the 33 patients had tumors with a T790M ratio of >= 0.4. The osimertinib response rate was significantly higher (92.3%) in patients with a T790M ratio of >= 0.4 than in those with a T790M ratio of < 0.4 (52.6%; p = 0.0237). We examined the correlation between the T790M ratio and the tumor reduction rate and obtained a coefficient of r = 0.417 (p = 0.0175). In patients with a T790M ratio of >= 0.4, the median progression-free survival was 355 days, which was longer, but not significant, than that in patients with a T790M ratio of < 0.4 (median: 264 days). In patients with a T790M ratio of >= 0.4, the median treatment duration from first-line therapy onward was 931 days, which was significantly longer than that in patients with a T790M ratio of < 0.4 (median, 567.5 days) (p = 0.044).Conclusion: The T790M ratio to EGFR activating mutation in tumor may correlate with the response to osimertinib, and patients with a higher T790M ratio have a longer treatment history.