Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

医学 彭布罗利珠单抗 内科学 肺癌 肿瘤科 化疗 性能状态 无进展生存期 癌症 免疫疗法
作者
Tony Mok,Yi−Long Wu,Iveta Kudaba,Dariusz M. Kowalski,Byoung Chul Cho,H.Z. Turna,Gilberto de Castro,Vichien Srimuninnimit,К. К. Лактионов,Igor Bondarenko,Kaoru Kubota,Gregory M. Lubiniecki,Jin Zhang,Debra Kush,Gilberto Lopes,Grigory Adamchuk,Myung‐Ju Ahn,Aurelia Alexandru,Özden Altundağ,Anna Alyasova
出处
期刊:The Lancet [Elsevier BV]
卷期号:393 (10183): 1819-1830 被引量:2795
标识
DOI:10.1016/s0140-6736(18)32409-7
摘要

First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894.From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively.The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.Merck Sharp & Dohme.
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
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
自觉的凌青完成签到,获得积分10
刚刚
刚刚
刚刚
一定要顺利毕业呀完成签到,获得积分10
1秒前
山河发布了新的文献求助10
1秒前
Noneone110完成签到,获得积分10
1秒前
这个郭我背了完成签到,获得积分10
1秒前
朝阳完成签到,获得积分10
2秒前
2秒前
SSS关注了科研通微信公众号
3秒前
浑语堂发布了新的文献求助10
3秒前
3秒前
kagura完成签到,获得积分10
4秒前
鹿见林发布了新的文献求助10
4秒前
lishan完成签到,获得积分10
6秒前
喜悦的鬼神完成签到 ,获得积分10
6秒前
仿若浮云完成签到,获得积分10
6秒前
jin完成签到,获得积分10
7秒前
丘比特应助称心太阳采纳,获得10
8秒前
9秒前
9秒前
9秒前
水泥酱发布了新的文献求助10
10秒前
烟花应助稳重的秋天采纳,获得10
11秒前
ohuo完成签到,获得积分10
11秒前
13秒前
13秒前
13秒前
14秒前
15秒前
15秒前
香蕉觅云应助鹿见林采纳,获得10
15秒前
小二郎应助鹿见林采纳,获得10
15秒前
星辰大海应助ll200207采纳,获得10
16秒前
CodeCraft应助科研进化中采纳,获得10
17秒前
17秒前
吉祥如意完成签到,获得积分10
18秒前
小鹿5460发布了新的文献求助10
19秒前
19秒前
yyyyyyyyr完成签到,获得积分20
20秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Conference Record, IAS Annual Meeting 1977 1250
Neuromuscular and Electrodiagnostic Medicine Board Review 1000
APA educational psychology handbook, Vol 1: Theories, constructs, and critical issues 700
An Annotated Checklist of Dinosaur Species by Continent 500
岡本唐貴自伝的回想画集 500
Distinct Aggregation Behaviors and Rheological Responses of Two Terminally Functionalized Polyisoprenes with Different Quadruple Hydrogen Bonding Motifs 450
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 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3652029
求助须知:如何正确求助?哪些是违规求助? 3216197
关于积分的说明 9711172
捐赠科研通 2924058
什么是DOI,文献DOI怎么找? 1601466
邀请新用户注册赠送积分活动 754190
科研通“疑难数据库(出版商)”最低求助积分说明 732987