Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Int J Cancer. 2019 Jun 1;144(11):2880-2886. doi: 10.1002/ijc.32015. Epub 2019 Jan 3.
Primary epidermal growth factor receptor (EGFR) T790M mutation can be occasionally identified in previous untreated nonsmall cell lung cancer (NSCLC) patients. To compare clinical characteristics and outcomes in patients with primary and acquired EGFR T790M mutation, we collected the data of patients diagnosed with EGFR mutation from 2012 to 2017 in Shanghai Chest Hospital. Primary EGFR T790M mutation was identified in 61 patients (1.1%; 95% confidence interval (CI): 0.8%-1.3%) of 5685 TKI-naive EGFR mutant patients. Acquired T790M mutation was detected in 98 patients (50.3%; 95%CI: 43.2%-57.3%) of 195 TKI-treated patients. T790M mutation always coexisted with sensitizing EGFR mutations. Primary EGFR T790M always coexisted with 21L858R (46/61) whereas acquired T790M coexisted with 19del (68/98), (p < 0.001). Among them, 18 patients with primary T790M mutation received osimertinib and 72 patients with acquired T790M mutation received osimertinib. The median progression-free survival (PFS) of osimertinib was significantly longer in primary T790M group (17.0 months, 95%CI:14.0-20.0 months) compared to acquired T790M group (10.0 months, 95%CI:8.6-11.4 months, p = 0.022). However, the median overall survival (OS) of acquired T790M mutation patients was significantly longer compared to that of primary T790M mutation patients who received osimertinib (50.4 months vs. 29.9 months, p = 0.016). Our findings suggest that primary T790M mutation likely coexists with 21L858R while acquired mutation likely coexists with 19del. Both mutations showed good response to osimertinib. Patients with primary T790M mutation experienced greater benefits from osimertinib. However, patients with acquired T790M mutation had a better overall survival during the entire clinical treatment.
原发性表皮生长因子受体（EGFR）T790M 突变偶尔可在未经治疗的非小细胞肺癌（NSCLC）患者中发现。为了比较原发性和获得性 EGFR T790M 突变患者的临床特征和结局，我们收集了 2012 年至 2017 年在上海胸科医院确诊 EGFR 突变患者的数据。在 5685 例未接受 TKI 治疗的 EGFR 突变患者中，原发性 EGFR T790M 突变患者 61 例（1.1%；95%置信区间[CI]：0.8%-1.3%）。在 195 例接受 TKI 治疗的患者中，检测到获得性 T790M 突变 98 例（50.3%；95%CI：43.2%-57.3%）。T790M 突变总是与敏感 EGFR 突变共存。原发性 EGFR T790M 总是与 21L858R 共存（46/61），而获得性 T790M 与 19del 共存（68/98），（p < 0.001）。其中，18 例原发性 T790M 突变患者接受奥希替尼治疗，72 例获得性 T790M 突变患者接受奥希替尼治疗。原发性 T790M 组的中位无进展生存期（PFS）明显长于获得性 T790M 组（17.0 个月，95%CI：14.0-20.0 个月）（p = 0.022）。然而，获得性 T790M 突变患者的中位总生存期（OS）明显长于接受奥希替尼治疗的原发性 T790M 突变患者（50.4 个月比 29.9 个月，p = 0.016）。我们的研究结果表明，原发性 T790M 突变可能与 21L858R 共存，而获得性突变可能与 19del 共存。两种突变对奥希替尼均有良好的反应。原发性 T790M 突变患者从奥希替尼中获益更大。然而，获得性 T790M 突变患者在整个临床治疗过程中总生存更好。
