Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)‒mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR‒tyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.

中文翻译：

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肺腺癌患者对一线表皮生长因子受体酪氨酸激酶抑制剂耐药后获得性T790M突变与临床特征的相关性

目的 本研究的主要目的是探讨一线EGFR-酪氨酸激酶抑制剂（TKI）治疗后获得性耐药的晚期表皮生长因子受体（EGFR）-突变型肺腺癌患者临床特征与T790M突变频率的关系。 . 材料和方法 我们招募了 EGFR 突变 IIIB-IV 期肺腺癌患者，这些患者已经进展到先前的 EGFR-TKI 治疗，并评估了他们的再活检 EGFR 突变状态。结果共纳入205例患者进行分析。再活检的总体 T790M 突变率为 46.3%。外显子19缺失突变、外显子21 L858R点突变和其他突变患者的T790M突变率分别为55.0%、37.3%和27.3%。基线外显子 19 缺失与显着更高的 T790M 突变频率相关（调整后的优势比，2.14；95% 置信区间 [CI]，1.20 至 3.83；p=0.010）。在外显子 19 缺失亚组中，Del E746-A750 突变患者的 T790M 突变发生率高于其他外显子 19 缺失亚型（61.6% 对 40.6%；优势比，2.35；95% CI，1.01 至 5.49） ；p=0.049）。一线 TKI 治疗的无进展生存期 (PFS) > 11 个月也与较高的 T790M 突变率相关（54.1% 与 39.3%；调整后的比值比，1.82；95% CI，1.02 至 3.25；p= 0.044）。在转移部位接受再活检的患者有更多机会携带 T790M 突变（52.6% 与 33.8%；调整后的比值比，1.97；95% CI，1.06 至 3.67；p=0.032）。结论 一线 EGFR-TKI、再活检部位、