T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients
T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients
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DOI：
10.1016/j.lungcan.2014.03.011
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发表时间：
2014-06-01
期刊：
影响因子：
5.3
通讯作者：
Schmid-Bindert, Gerald
中科院分区：
文献类型：
--
作者：
Li, Wei;Ren, Shengxiang;Schmid-Bindert, Gerald
背景和目的：持续的EGFR-TKI治疗对一些对EGFR-TKI有获得性耐药的患者显示出良好的疗效。本研究旨在探讨进展期继发性T790M突变与EGFR-TKI治疗进展后疗效的相关性。方法：从2011年3月至2013年3月，在同济大学肿瘤研究所进行再次活检的晚期非小细胞肺癌患者对EGFR-TKI产生获得性耐药。结果：54例患者按RECIST标准，中位无进展生存时间(PFS1)为10.9个月。总体而言，53.7%(29/54)的患者在EGFR-TKIs失败后出现T790M突变；T790M突变患者和无突变患者之间的Pfs1差异无统计学意义(13.0vs.10.5个月，p=0.894)。总共有41名患者接受了超越进展的TKI治疗，其中22名局部进展接受额外的局部治疗，19名逐步进展接受额外的化疗。接受EGFR-TKI超越进展治疗的患者的中位无进展生存时间为3.5月(95%CI，2.689-4.311)。携带T790M突变的患者较无突变患者的PfS2(6.3月vs.2.6月，p=0.002)和总生存期(39.8vs.23.2月，p=0.044)显著延长。结论：与未发生T790M突变的患者相比，进展期继发T790M突变患者在获得EGFR-TKI耐药后出现渐进性或局部性进展的患者比未发生T790M突变的患者受益更多。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Background and purpose: Continuous EGFR-TKI treatment beyond progression has shown promising benefit for some patients with acquired resistance to EGFR-TKIs. The aim of this study was to investigate the association of secondary T790M mutation at the time of progression with the efficacy of EGFR-TKI treatment beyond progression.Methods: From March 2011 to March 2013, patients with advanced NSCLC who developed acquired resistance to EGFR-TKI and where a re-biopsy was performed at Tongji University Cancer Institute were included into this study. Scorpion ARMS was used to detect EGFR mutation status.Results: A total of 54 patients were enrolled in this study with a median progression-free survival time (PFS1) of 10.9 months according to RECIST criteria. In all, 53.7% (29/54) had T790M mutation after the failure of EGFR-TKIs; PFS1 was not statistically significantly different between patients with T790M mutation and without (13.0 vs. 10.5 months, p = 0.894). In all, 41 patients received TKI treatment beyond progression, including 22 with local progression to receive additional local therapy and 19 with gradual progression to receive additional chemotherapy. The median progression-free survival time (PFS2) of patients who received EGFR-TKI beyond progression treatment was 3.5 months (95% CI, 2.689-4.311). Patients with T790M mutation had significantly longer PFS2 (6.3 vs. 2.6 months, p = 0.002) and overall survival (39.8 vs. 23.2 months, p = 0.044) than those without.Conclusion: Patients with secondary T790M mutation at the time of progression having gradual or local progression after acquired resistance to EGFR-TKI benefit more from EGFR-TKI treatment beyond progression compared to those without T790M mutation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.