Association of Exon 19 and 21 EGFR Mutation Patterns with Treatment Outcome after First-Line Tyrosine Kinase Inhibitor in Metastatic Non-Small-Cell Lung Cancer
Association of Exon 19 and 21 EGFR Mutation Patterns with Treatment Outcome after First-Line Tyrosine Kinase Inhibitor in Metastatic Non-Small-Cell Lung Cancer
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DOI：
10.1097/jto.0b013e31829f684a
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发表时间：
2013-09-01
影响因子：
20.4
通讯作者：
Wong, Maria P.
中科院分区：
文献类型：
--
作者：
Lee, Victor H. F.;Tin, Vicky P. C.;Wong, Maria P.
背景：本研究调查了表皮生长因子受体（EGFR）外显子 19 和外显子 21 不同亚型突变的转移性非小细胞肺癌患者一线酪氨酸激酶抑制剂（TKI）的生存结果是否存在差异。方法：在 452 名 IIIB 和 IV 期非小细胞肺癌患者中，192 名患者（42.5%）携带 EGFR 突变，170 名患者携带 EGFR 突变。 (37.5%) 接受 TKI 作为一线治疗。通过直接测序进行EGFR突变分析。比较了这 170 名患者中外显子 19 和外显子 21 EGFR 突变不同亚型的生存和缓解结果。结果：携带外显子 19 18 核苷酸缺失 (delL747_P753insS) 的患者的中位无进展生存期 (PFS) 最短（6.5 个月），其次是 15 核苷酸缺失 (delE746_A750) 的患者 (12.4)月）和混合插入/替换突变（22.3 个月；p = 0.012）。然而，从密码子 E746 开始进行外显子 19 缺失的患者比从 L747 开始的患者具有更好的中位 PFS（14.2 个月）（6.5 个月；风险比，0.445；95% 置信区间 [0.219-0.903]；p = 0.021）。此外，外显子 21 L858R 比 L861R/L861Q 获得更长的中位 PFS（分别为 11.4 个月与 2.1 个月；风险比，0.298；95% 置信区间 [0.090-0.980]；p = 0.034）。结论：EGFR 外显子 19 和 21 突变的不同亚型与一线 TKI 的生存率存在差异治疗。外显子 19 缺失的详细序列评估可能为 TKI 后生存结果提供重要的预后信息。
Background:This study investigated whether there were differential survival outcomes to first-line tyrosine kinase inhibitors (TKI) in patients with metastatic non-small-cell lung cancer harboring different subtypes of exon 19 and exon 21 mutations on epidermal growth factor receptor (EGFR).Methods:Of 452 patients with stage IIIB and IV non-small-cell lung cancer, 192 patients (42.5%) harbored EGFR mutation and 170 (37.5%) received TKI as first-line treatment. EGFR mutation analysis was performed by direct sequencing. Survival and response outcome were compared among different subtypes of exon 19 and exon 21 EGFR mutations in these 170 patients.Results:Patients harboring exon 19 18-nucleotide deletion (delL747_P753insS) had the shortest median progression-free survival (PFS) (6.5 months), followed by those with 15-nucleotide deletion (delE746_A750) (12.4 months) and mixed insertion/substitution mutations (22.3 months; p = 0.012). However, patients who had exon 19 deletions starting on codon E746 had better median PFS (14.2 months) than those starting on L747 (6.5 months; hazard ratio, 0.445; 95% confidence interval [0.219-0.903]; p = 0.021). Besides, exon 21 L858R derived a longer median PFS than L861R/L861Q (11.4 months versus 2.1 months, respectively; hazard ratio, 0.298; 95% confidence interval [0.090-0.980]; p = 0.034).Conclusions:Different subtypes of EGFR exon 19 and 21 mutations exhibited differential survival to first-line TKI therapy. Detailed sequence evaluation of exon 19 deletions may provide important prognostic information on survival outcome after TKI.