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Association between advanced NSCLC T790 M EGFR-TKI secondary resistance and prognosis

机译:晚期NSCLC T790 M EGFR-TKI继发耐药与预后的关系

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摘要

Epidermal growth factor receptor (EGFR) mutations for EGFR-tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients are with clinical benefits. Nevertheless, eventual resistance to EGFR-TKI is almost inevitable. In about 50% patients, EGFR-TKI develops a secondary mutation, which is often the T790 M mutation. We aimed to investigate the relationship between EGFR gene status in the peripheral blood and prognosis (progression-free survival [PFS] and overall survival [OS]) in advanced lung adenocarcinoma patients and the 20 exon 790 site mutation (T790 M) and acquired resistance to EGFR-TKI.A total of 49 patients with EGFR-TKI resistance and advanced lung cancer who visited the Shihezi University School of Medicine between 12/2013 and 12/2014 were enrolled in this study. Peripheral blood plasma DNA was isolated after EGFR-TKI resistance and the EGFR exon 20 T790 M mutation was detected using the probe amplification refractory mutation system method.The T790 M mutation rate was 30.6% (15/49). There was no association between T790 M mutation and age, gender, smoking, clinical stage, Eastern Cooperative Oncology Group rating, initial EGFR mutation, and EGFR-TKI drugs, but EGFR-TKI resistance was associated with progression (P = .009). Median progression-free survival (PFS) of patients with T790 M mutation was 9.6 months and median overall survival (OS) was 17.6 months, compared to 6.8 and 12.7 months in controls (P = .018 and P = .027). Multivariate analysis showed that T790 M mutations independently affected the PFS (risk ratio, RR = 0.653, 95% confidence interval, CI: 0.069–0.886, P = .032) and OS (RR = 0.847, 95% CI: 0.208–2.696, P = .008).T790 M mutation and EGFR-TKI resistance are independent factors to affect PFS and OS of non-small cell lung cancer patients.
机译:非小细胞肺癌(NSCLC)患者中EGFR-酪氨酸激酶抑制剂(EGFR-TKI)的表皮生长因子受体(EGFR)突变具有临床益处。尽管如此,最终对EGFR-TKI的耐药性几乎是不可避免的。在约50%的患者中,EGFR-TKI发生继发突变,通常是T790 M突变。我们旨在研究晚期肺腺癌患者外周血EGFR基因状态与预后(无进展生存期[PFS]和总体生存期[OS])与20个外显子790位点突变(T790 M)和获得性耐药之间的关系。本研究纳入了在12/2013至12/2014年间访问石河子大学医学院的49例EGFR-TKI耐药和晚期肺癌患者。 EGFR-TKI耐药后分离外周血DNA,采用探针扩增难治性突变系统法检测EGFR外显子20 T790 M突变,T790 M突变率为30.6%(15/49)。 T790 M突变与年龄,性别,吸烟,临床分期,东部合作肿瘤小组评分,初始EGFR突变和EGFR-TKI药物之间无关联,但EGFR-TKI耐药与进展相关(P = .009)。 T790 M突变患者的中位无进展生存期(PFS)为9.6个月,中位总体生存期(OS)为17.6个月,而对照组为6.8和12.7个月(P = .018和P = .027)。多变量分析显示,T790 M突变独立影响PFS(风险比,RR = 0.653,95%置信区间,CI:0.069-0.886,P = .032)和OS(RR = 0.847,95%CI:0.208-2.696, P = .008).T790 M突变和EGFR-TKI耐药是影响非小细胞肺癌患者PFS和OS的独立因素。

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