OBJECTIVES Advanced non-small cell lung cancer (NSCLC) patients harboring non-resistant uncommon epidermal growth factor receptor (EGFR) mutations have stepped into the era of targeted therapy. This study aimed to investigate the incidence of acquired T790M mutation and their outcome to subsequent osimertinib in patients of advanced NSCLC harboring uncommon EGFR mutations. PATIENTS AND METHODS Patients with EGFR mutation and performed re-biopsy after progression on prior EGFR-tyrosine kinase inhibitors (TKIs) were reviewed and analyzed. Those with T790M mutation and received subsequent osimertinib treatment were further collected for survival analysis. RESULTS Finally, 754 patients, including 48 with uncommon mutation, 362 with 19del and 344 with L858R were enrolled. T790M mutation was identified in 341 patients (341/754, 45.2 %). The incidence of T790M mutation was 27.1 % in patients harboring uncommon mutations, significantly lower than 55.2 % and 37.2 % of 19del and L858R (p < 0.001). Logistic regression analysis further found uncommon mutation associated with significantly lower probability of developing T790M (odds ratio [OR] = 0.32, 95 % confidence interval [CI] 0.16-0.64). Among 236 patients received subsequent osimertinib treatment (including 12 uncommon mutation, 145 19del and 79 L858R), patients harboring uncommon mutations showed significantly shorter progression free survival (PFS) (median: 4.6 vs. 11.6 vs. 12.1 months, p < 0.001) and overall survival (OS) (median: 8.1 vs. 35.4 vs. 24.9 months, p = 0.001) compared with 19del and L858R, also associated with numerically lower objective response rate (ORR) (p = 0.085) and lower disease control rate (DCR) (p = 0.074). Multivariate analysis further found that uncommon mutation was the only one significantly associated with both PFS (hazard ratio [HR] = 3.44, 95 %CI 1.79-6.58) and OS (HR = 3.64, 95 %CI 1.66-7.99). CONCLUSIONS Uncommon EGFR mutation showed a significantly lower incidence of acquired T790M mutation and benefited significantly less from subsequent osimertinib treatment than common EGFR mutations in patients with advanced NSCLC.

中文翻译：

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EGFR-TKI治疗后晚期NSCLC患者中罕见的EGFR突变与T790M突变发生率降低相关。

目的携带非耐药性罕见表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）患者已进入靶向治疗时代。这项研究旨在调查具有罕见EGFR突变的晚期NSCLC患者获得性T790M突变的发生率及其对随后的osimertinib的预后。病人和方法对具有EGFR突变并在先前的EGFR-酪氨酸激酶抑制剂（TKIs）进展后进行了活检的患者进行了回顾和分析。进一步收集具有T790M突变并接受了后续奥西替尼治疗的患者进行生存分析。结果最后纳入了754例患者，包括48例罕见突变，362例19del和344例L858R。在341例患者中发现了T790M突变（341/754，45.2％）。携带罕见突变的患者中T790M突变的发生率为27.1％，显着低于19del和L858R的55.2％和37.2％（p <0.001）。Logistic回归分析进一步发现罕见突变与发展T790M的可能性显着降低有关（赔率[OR] = 0.32，95％置信区间[CI] 0.16-0.64）。在236例接受后续奥西替尼治疗的患者中（包括12个罕见突变，145个19del和79个L858R），具有罕见突变的患者表现出无进展生存期（PFS）明显缩短（中位数：4.6 vs. 11.6 vs. 12.1个月，p <0.001）和与19del和L858R相比，总体生存（OS）（中位数：8.1 vs. 35.4 vs. 24.9个月，p = 0.001），也与客观较低的客观反应率（ORR）相关（p = 0。085）和较低的疾病控制率（DCR）（p = 0.074）。多变量分析进一步发现，罕见突变是与PFS（危险比[HR] = 3.44，95％CI 1.79-6.58）和OS（HR = 3.64，95％CI 1.66-7.99）均显着相关的唯一突变。结论晚期NSCLC患者中罕见的EGFR突变显示获得性T790M突变的发生率显着降低，并且从随后的osimertinib治疗中获得的收益明显少于常见的EGFR突变。