T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients

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• 作者：Wei Li^a ; ¹ ; Shengxiang Ren^a ; ¹ ; Jiayu Li^a ; Aiwu Li^a ; Lihong Fan^a ; Xuefei Li^b ; Cao Zhao^b ; Yayi He^a ; Guanghui Gao^a ; Xiaoxia Chen^a ; Shuai Li^a ; Jingyun Shi^c ; ; Caicun Zhou^a ; ^{caicunzhoudr@163.com" class="auth_mail} ; Ke Fei^d ; Gerald Schmid-Bindert^e
• 关键词：NSCLC ; EGFR-TKI ; Acquired assistance ; Secondary T790M mutation
• 刊名：Lung Cancer
• 出版年：June 2014
• 年：2014
• 卷：84
• 期：3
• 页码：295-300
• 全文大小：905 K

文摘

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.