Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

医学 培美曲塞 卡铂 肺癌 内科学 实体瘤疗效评价标准 安慰剂 肿瘤科 彭布罗利珠单抗 癌症 化疗 外科 进行性疾病 顺铂 病理 免疫疗法 替代医学
作者
Marina Chiara Garassino,Shirish M. Gadgeel,Emilio Esteban,Enriqueta Felip,Giovanna Speranza,Manuel Dómine,Maximilian J. Hochmair,Steven Powell,Susanna Y. Cheng,Helge Bischoff,Nir Peled,Martin Reck,Rina Hui,Edward B. Garon,Michael Boyer,Ziwen Wei,Thomas Burke,M. Catherine Pietanza,Delvys Rodríguez‐Abreu
出处
期刊:Lancet Oncology [Elsevier BV]
卷期号:21 (3): 387-397 被引量:185
标识
DOI:10.1016/s1470-2045(19)30801-0
摘要

Background Pembrolizumab plus pemetrexed–platinum led to superior overall survival and progression-free survival, and a higher proportion of patients with a confirmed complete or partial response over placebo plus pemetrexed–platinum in the KEYNOTE-189 study. We aimed to evaluate prespecified exploratory patient-reported outcomes (PROs) in patients in KEYNOTE-189. Methods In the multicentre, double-blind, randomised, placebo-controlled, phase 3 KEYNOTE-189 study done at 126 cancer centres in 16 countries, eligible patients aged 18 years or older with histologically or cytologically confirmed metastatic non-squamous non-small-cell lung cancer without sensitising EGFR or ALK alterations, measurable disease as per Response Evaluation Criteria in Solid Tumors (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled. Patients were randomly assigned (2:1) to receive intravenous pembrolizumab (200 mg) or saline placebo every 3 weeks for up to 2 years (35 cycles); all patients received four cycles of intravenous pemetrexed (500 mg/m2) with carboplatin (5 mg/mL per min) or cisplatin (75 mg/m2; investigator's choice) every 3 weeks for four cycles, followed by pemetrexed maintenance therapy every 3 weeks. Permuted block randomisation (block size six) was done with an interactive voice-response system and stratified by PD-L1 expression, choice of platinum, and smoking status. Patients, investigators, and other study personnel were unaware of treatment assignment. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13) were administered at cycles 1–5, every three cycles thereafter during year 1, and every four cycles during years 2–3. The primary endpoints (overall survival and progression-free survival) have been published previously. Key PRO endpoints were change from baseline to week 12 (during chemotherapy) and week 21 (following chemotherapy) in QLQ-C30 global health status/quality of life (GHS/QOL) score, and time to deterioration in cough, chest pain, or dyspnoea. PROs were analysed in all randomly assigned patients who received at least one dose of study medication and who completed at least one PRO assessment, and the results are provided with two-sided, nominal p values. This ongoing study is registered with ClinicalTrials.gov, number NCT02578680. Findings Between Feb 26, 2016, and March 6, 2017, 616 patients were enrolled; median follow-up was 10·5 months (range 0·2–20·4) as of data cutoff on Nov 8, 2017. 402 (99%) of 405 patients in the pembrolizumab plus pemetrexed–platinum group and 200 (99%) of 202 patients in the placebo plus pemetrexed–platinum-treated group completed at least one PRO assessment. At baseline, 359 (89%) of 402 patients in the pembrolizumab plus pemetrexed–platinum group and 180 (90%) of 200 in the placebo plus pemetrexed–platinum group were compliant with QLQ-C30; at week 12, 319 (90%) of 354 and 149 (89%) of 167 patients were compliant, respectively; and at week 21, 249 (76%) of 326 and 91 (64%) of 143 patients were compliant, respectively. From baseline to week 12, GHS/QOL scores were maintained with both pembrolizumab plus pemetrexed–platinum (least-squares mean change: 1·0 point [95% CI −1·3 to 3·2] increase) and placebo plus pemetrexed–platinum (−2·6 points [−5·8 to 0·5] decrease; between-group difference: 3·6 points [−0·1 to 7·2]; p=0·053). From baseline to week 21, GHS/QOL scores were better maintained with pembrolizumab plus pemetrexed–platinum (least-squares mean change: 1·3 points [95% CI −1·2 to 3·6] increase) than with placebo plus pemetrexed–platinum (−4·0 points [−7·7 to −0·3] decrease; between-group difference: 5·3 points [1·1 to 9·5]; p=0·014). Median time to deterioration in cough, chest pain, or dyspnoea was not reached (95% CI 10·2 months to not reached) with pembrolizumab plus pemetrexed–platinum, and was 7·0 months (4·8 months to not reached) with placebo plus pemetrexed–platinum (hazard ratio 0·81 [95% CI 0·60–1·09], p=0·16). Interpretation The addition of pembrolizumab to standard chemotherapy maintained GHS/QOL, with improved GHS/QOL scores at week 21 in the pembrolizumab plus chemotherapy group compared with the placebo plus chemotherapy group. These data further support use of pembrolizumab plus pemetrexed–platinum as first-line therapy for patients with metastatic non-squamous non-small-cell lung cancer. Funding 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
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
刚刚
moxi摩西完成签到,获得积分10
刚刚
卷卷完成签到,获得积分10
2秒前
时笙发布了新的文献求助10
3秒前
3秒前
pterion完成签到,获得积分10
3秒前
3秒前
5秒前
哒哒完成签到,获得积分10
7秒前
7秒前
循环发布了新的文献求助10
7秒前
幽默毛衣发布了新的文献求助10
10秒前
12秒前
循环完成签到,获得积分10
12秒前
leanne发布了新的文献求助10
12秒前
13秒前
量子星尘发布了新的文献求助10
13秒前
14秒前
14秒前
开灯人和关灯人完成签到,获得积分20
15秒前
Stardust发布了新的文献求助10
16秒前
17秒前
FashionBoy应助爱笑晓曼采纳,获得10
18秒前
张雯思发布了新的文献求助10
19秒前
Priority完成签到,获得积分10
20秒前
光热效应发布了新的文献求助30
20秒前
风之星给风之星的求助进行了留言
20秒前
20秒前
ASH发布了新的文献求助10
20秒前
OxO完成签到,获得积分10
20秒前
21秒前
搜集达人应助快乐一江采纳,获得10
21秒前
22秒前
leanne完成签到,获得积分20
23秒前
幽默毛衣完成签到,获得积分10
24秒前
晨曦完成签到,获得积分10
24秒前
延文星发布了新的文献求助10
26秒前
张雯思发布了新的文献求助10
27秒前
27秒前
隐形曼青应助Stardust采纳,获得10
30秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 3989390
求助须知:如何正确求助?哪些是违规求助? 3531487
关于积分的说明 11254109
捐赠科研通 3270153
什么是DOI,文献DOI怎么找? 1804887
邀请新用户注册赠送积分活动 882087
科研通“疑难数据库(出版商)”最低求助积分说明 809174