登录  注册
肿瘤学学术中心首页 > 期刊 > 中国作者重要发表

肿瘤学学术中心

阿法替尼治疗携带EGFR少见突变晚期非小细胞肺癌患者的临床疗效:LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6研究的综合析因分析

Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: A combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6

来源:Scopus 发布时间:2015-8-28
作者:Yang, J.C.-H., Sequist, L.V., Geater, S.L., Tsai, C.-M., Mok, T.S.K., Schuler, M., Yamamoto, N., Yu, C.-J., Ou, S.H.I., Zhou, C., Massey, D., Zazulina, V., Wu, Y.-L.
机构: 台湾大学医学院
期刊: LANCET ONCOL2015年7月期卷

Background: Most patients with non-small-cell lung cancer tumours that have EGFR mutations have deletion mutations in exon 19 or the Leu858Arg point mutation in exon 21, or both (ie, common mutations). However, a subset of patients (10%) with mutations in EGFR have tumours that harbour uncommon mutations. There is a paucity of data regarding the sensitivity of these tumours to EGFR inhibitors. Here we present data for the activity of afatinib in patients with advanced non-small-cell lung cancer that have tumours harbouring uncommon EGFR mutations. Methods: In this post-hoc analysis, we used prospectively collected data from tyrosine kinase inhibitor-naive patients with EGFR mutation-positive advanced (stage IIIb-IV) lung adenocarcinomas who were given afatinib in a single group phase 2 trial (LUX-Lung 2), and randomised phase 3 trials (LUX-Lung 3 and LUX-Lung 6). Analyses were done in the intention-to-treat population, including all randomly assigned patients with uncommon EGFR mutations. The type of EGFR mutation (exon 19 deletion [del19], Leu858Arg point mutation in exon 21, or other) and ethnic origin (LUX-Lung 3 only; Asian vs non-Asian) were pre-specified stratification factors in the randomised trials. We categorised all uncommon mutations as: point mutations or duplications in exons 18-21 (group 1); de-novo Thr790Met mutations in exon 20 alone or in combination with other mutations (group 2); or exon 20 insertions (group 3). We also assessed outcomes in patients with the most frequent uncommon mutations, Gly719Xaa, Leu861Gln, and Ser768Ile, alone or in combination with other mutations. Response was established by independent radiological review. These trials are registered with ClinicalTrials.gov, numbers NCT00525148, NCT00949650, and NCT01121393. Findings: Of 600 patients given afatinib across the three trials, 75 (12%) patients had uncommon EGFR mutations (38 in group 1, 14 in group 2, 23 in group 3). 27 (71·1%, 95% CI 54·1-84·6) patients in group 1 had objective responses, as did two (14·3%, 1·8-42·8) in group 2 and two (8·7%, 1·1-28·0) in group 3. Median progression-free survival was 10·7 months (95% CI 5·6-14·7) in group 1, 2·9 months (1·2-8·3) in group 2; and 2·7 months (1·8-4·2) in group 3. Median overall survival was 19·4 months (95% CI 16·4-26·9) in group 1, 14·9 months (8·1-24·9) in group 2, and 9·2 months (4·1-14·2) in group 3. For the most frequent uncommon mutations, 14 (77·8%, 95% CI 52·4-93·6) patients with Gly719Xaa had an objective response, as did nine (56·3%, 29·9-80·2) with Leu861Gln, and eight (100·0%, 63·1-100·0) with Ser768Ile. Interpretation: Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types. Clinical benefit was lower in patients with de-novo Thr790Met and exon 20 insertion mutations. These data could help inform clinical decisions for patients with non-small-cell lung cancer harbouring uncommon EGFR mutations. Funding: Boehringer Ingelheim. © 2015 Elsevier Ltd.

通讯作者:Graduate Institute of Oncology, National Taiwan University and National Taiwan University Hospital, Taiwan
顶一下(0

发表评论

学科影响因子排名more

 会议回顾 more

  • 中文版启动会暨第一次编委会议 圆满...

  • 【专题】2015年美国临床肿瘤大会...

  • 多模式防治 改善肿瘤患者生存

 热门病例 more

 热门指南  more

Elsevier中国网站
爱唯医学网
爱思唯尔科技部
NursingChina
柳叶刀中文版
大通医疗决策
医大爱思唯尔
Elsevier医学数据库
CK
Journal Consult
Procedures_CONSULT
ClinicalPharmacologyLogo
3D Interact Anatomy
Mosby’s Nursing Consult
NursingChina
Science Direct