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三种主要酪氨酸激酶抑制剂作为表皮生长因子受体突变的非小细胞肺癌一线治疗效果的比较。

Comparison of the effects of the three major tyrosine kinase inhibitors as first-line therapy for non-small-cell lung cancer harboring epidermal growth factor receptor mutations.

作者信息

Tu Chih-Yen, Chen Chuan-Mu, Liao Wei-Chih, Wu Biing-Ru, Chen Chih-Yu, Chen Wei-Chun, Hsia Te-Chun, Cheng Wen-Chien, Chen Chia-Hung

机构信息

Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

出版信息

Oncotarget. 2018 Feb 4;9(36):24237-24247. doi: 10.18632/oncotarget.24386. eCollection 2018 May 11.

Abstract

INTRODUCTION

Patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR)-activating mutations have good response rate and longer progression-free survival (PFS) when treated with the tyrosine kinase inhibitors (TKI) compared with platinum-based chemotherapy. However, studies comparing the effectiveness of these drugs as first-line therapy in such patients are limited.

RESULTS

We analyzed 422 patients with EGFR-mutated advanced lung adenocarcinoma receiving first-line gefitinib ( = 195, 46.2%), erlotinib ( = 123, 29.1%), or afatinib ( = 104, 24.6%). The PFS of the afatinib group was longer (12.2 months) than that of the gefitinib group (9.8 months) ( = 0.035) but similar to that of the erlotinib group (11.4 months) ( = 0.38). In patients without brain metastasis (BM), subgroup analysis showed that the afatinib group had significantly longer PFS (13.1 months) than erlotinib (11.7 months) and gefitinib (9.8 months) groups ( = 0.010). Patients with exon 19 deletions in the afatinib and erlotinib groups had potentially long PFS ( = 0.073). Efficacy of afatinib was similar between the 30 mg and 40 mg arms (median PFS 16.1 months vs. 10.3 months; = 0.923).

CONCLUSIONS

Afatinib may be the optimal EGFR-TKI for advanced lung adenocarcinoma harboring EGFR-activating mutations, particularly in the absence of BM. Patients with exon 19 deletions taking afatinib had potentially long PFS. An afatinib dose of 30 and 40 mg has similar effect.

METHODS

We conducted this retrospective study at a single medical center from January 2013 to March 2017 and used PFS to evaluate the effectiveness of gefitinib, erlotinib, and afatinib in patients with advanced lung adenocarcinoma harboring EGFR mutations.

摘要

引言

与铂类化疗相比,携带表皮生长因子受体(EGFR)激活突变的晚期肺腺癌患者接受酪氨酸激酶抑制剂(TKI)治疗时,缓解率良好且无进展生存期(PFS)更长。然而,比较这些药物作为此类患者一线治疗有效性的研究有限。

结果

我们分析了422例接受一线吉非替尼(n = 195,46.2%)、厄洛替尼(n = 123,29.1%)或阿法替尼(n = 104,24.6%)治疗的EGFR突变晚期肺腺癌患者。阿法替尼组的PFS(12.2个月)长于吉非替尼组(9.8个月)(P = 0.035),但与厄洛替尼组(11.4个月)相似(P = 0.38)。在无脑转移(BM)的患者中,亚组分析显示阿法替尼组的PFS(13.1个月)显著长于厄洛替尼组(11.7个月)和吉非替尼组(9.8个月)(P = 0.010)。阿法替尼组和厄洛替尼组中发生19外显子缺失的患者PFS可能较长(P = 0.073)。阿法替尼30 mg和40 mg剂量组的疗效相似(中位PFS 16.1个月对10.3个月;P = 0.923)。

结论

阿法替尼可能是携带EGFR激活突变的晚期肺腺癌的最佳EGFR-TKI,尤其是在无BM的情况下。接受阿法替尼治疗的19外显子缺失患者PFS可能较长。阿法替尼30 mg和40 mg剂量的疗效相似。

方法

我们于2013年1月至2017年3月在单一医疗中心进行了这项回顾性研究,并使用PFS评估吉非替尼、厄洛替尼和阿法替尼对携带EGFR突变的晚期肺腺癌患者的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/040c/5966263/6594e26a910e/oncotarget-09-24237-g001.jpg

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