Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial

医学 吉非替尼 内科学 临床终点 中止 人口 肺癌 肿瘤科 表皮生长因子受体 危险系数 无进展生存期 非小细胞肺癌 随机对照试验 癌症 置信区间 化疗 环境卫生 A549电池
作者
Yi‐Long Wu,Ying Cheng,Xiangdong Zhou,Ki Hyeong Lee,Kazuhiko Nakagawa,Seiji Niho,Fumito Tsuji,R. Linke,Rafael Rosell,J. Corral,Maria Rita Migliorino,Adam Płużański,Eric Sbar,Tao Wang,Jane Liang White,Sashi Nadanaciva,Rickard Sandin,Tony Mok
出处
期刊:Lancet Oncology [Elsevier BV]
卷期号:18 (11): 1454-1466 被引量:1061
标识
DOI:10.1016/s1470-2045(17)30608-3
摘要

Background Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC). Methods In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions. We randomly assigned participants (1:1) to receive oral dacomitinib 45 mg/day (in 28-day cycles) or oral gefitinib 250 mg/day (in 28-day cycles) until disease progression or another discontinuation criterion was met. Randomisation, stratified by race and EGFR mutation type, was done with a computer-generated random code assigned by a central interactive web response system. The primary endpoint was progression-free survival assessed by masked independent review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01774721, and is ongoing but no longer recruiting patients. Findings Between May 9, 2013, and March 20, 2015, 452 eligible patients were randomly assigned to receive dacomitinib (n=227) or gefitinib (n=225). Median duration of follow-up for progression-free survival was 22·1 months (95% CI 20·3–23·9). Median progression-free survival according to masked independent review was 14·7 months (95% CI 11·1–16·6) in the dacomitinib group and 9·2 months (9·1–11·0) in the gefitinib group (hazard ratio 0·59, 95% CI 0·47–0·74; p<0·0001). The most common grade 3–4 adverse events were dermatitis acneiform (31 [14%] of 227 patients given dacomitinib vs none of 224 patients given gefitinib), diarrhoea (19 [8%] vs two [1%]), and raised alanine aminotransferase levels (two [1%] vs 19 [8%]). Treatment-related serious adverse events were reported in 21 (9%) patients given dacomitinib and in ten (4%) patients given gefitinib. Two treatment-related deaths occurred in the dacomitinib group (one related to untreated diarrhoea and one to untreated cholelithases/liver disease) and one in the gefitinib group (related to sigmoid colon diverticulitis/rupture complicated by pneumonia). Interpretation Dacomitinib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population. Funding SFJ Pharmaceuticals Group and Pfizer.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
LHT发布了新的文献求助10
刚刚
落后乐荷完成签到,获得积分10
1秒前
piaoaxi完成签到 ,获得积分10
1秒前
妮妮完成签到,获得积分10
2秒前
前进中完成签到,获得积分10
3秒前
韭菜盒子发布了新的文献求助10
4秒前
4秒前
Q22发布了新的文献求助10
4秒前
鲁丁丁完成签到 ,获得积分10
5秒前
jason完成签到,获得积分10
6秒前
mike2012完成签到 ,获得积分10
6秒前
KINGAZX完成签到 ,获得积分10
9秒前
LHT完成签到,获得积分10
10秒前
研友_VZG7GZ应助韭菜盒子采纳,获得10
10秒前
CLY完成签到,获得积分10
12秒前
Q22完成签到,获得积分10
12秒前
weiyayayayayaya完成签到,获得积分10
12秒前
CAOHOU应助虚心的芹采纳,获得10
13秒前
折花几慕应助虚心的芹采纳,获得20
13秒前
折花几慕应助虚心的芹采纳,获得20
13秒前
大胆砖头完成签到 ,获得积分10
13秒前
celia完成签到 ,获得积分10
13秒前
Beyond095完成签到,获得积分10
14秒前
搜集达人应助Q22采纳,获得10
16秒前
16秒前
万能图书馆应助夏傥采纳,获得10
18秒前
研友_X894JZ完成签到 ,获得积分10
18秒前
量子星尘发布了新的文献求助10
19秒前
20秒前
宁静致远完成签到,获得积分10
21秒前
不知干嘛完成签到,获得积分10
23秒前
Grace159完成签到 ,获得积分10
25秒前
27秒前
hello完成签到,获得积分10
28秒前
韭菜盒子完成签到,获得积分20
28秒前
科研通AI2S应助欣慰妙海采纳,获得10
28秒前
张秉环完成签到 ,获得积分10
29秒前
白凌风完成签到 ,获得积分10
30秒前
脑洞疼应助张承诺采纳,获得10
31秒前
学术完成签到 ,获得积分10
31秒前
高分求助中
Semantics for Latin: An Introduction 1155
Genomic signature of non-random mating in human complex traits 1000
Plutonium Handbook 1000
Three plays : drama 1000
Robot-supported joining of reinforcement textiles with one-sided sewing heads 600
SPSS for Windows Step by Step: A Simple Study Guide and Reference, 17.0 Update (10th Edition) 500
Multimodal injustices: Speech acts, gender bias, and speaker’s status 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4106192
求助须知:如何正确求助?哪些是违规求助? 3644100
关于积分的说明 11542941
捐赠科研通 3351096
什么是DOI,文献DOI怎么找? 1841209
邀请新用户注册赠送积分活动 907950
科研通“疑难数据库(出版商)”最低求助积分说明 825090