Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial

医学 贝伐单抗 内科学 福尔菲里 伊立替康 彭布罗利珠单抗 肿瘤科 西妥昔单抗 奥沙利铂 临床终点 结直肠癌 人口 生活质量(医疗保健) 癌症 实体瘤疗效评价标准 氟尿嘧啶 无进展生存期 微卫星不稳定性 临床研究阶段 化疗 临床试验 环境卫生 化学 生物化学 免疫疗法 等位基因 护理部 基因 微卫星
作者
Thierry André,Mayur M. Amonkar,Josephine M. Norquist,Kai-Keen Shiu,Tae Won Kim,Benny Vittrup Jensen,Lars Henrik Jensen,Cornelis J.A. Punt,Denis Smith,Rocio García‐Carbonero,Isabel Sevilla,Christelle de la Fouchardière,Fernando Rivera,Elena Élez,Luis A. Díaz,Takayuki Yoshino,Eric Van Cutsem,Ping Yang,Mohammed Z.H. Farooqui,Dung T. Le
出处
期刊:Lancet Oncology [Elsevier BV]
卷期号:22 (5): 665-677 被引量:162
标识
DOI:10.1016/s1470-2045(21)00064-4
摘要

In the KEYNOTE-177 study, pembrolizumab monotherapy provided statistically significant and clinically meaningful improvements in progression-free survival versus chemotherapy as first-line treatment in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. To further support the efficacy and safety findings of the KEYNOTE-177 study, results of the health-related quality of life (HRQOL) analyses are reported here.KEYNOTE-177 is an open-label, randomised, phase 3 trial being done at 192 cancer centres in 23 countries, in patients aged 18 years and older with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had not received previous systemic therapy for metastatic disease. Eligible patients were randomly assigned (1:1) centrally by use of interactive voice response or integrated web response technology to receive pembrolizumab 200 mg intravenously every 3 weeks or investigator's choice chemotherapy (mFOLFOX6 [leucovorin, fluorouracil, and oxaliplatin] or FOLFIRI [leucovorin, fluorouracil, and irinotecan] intravenously every 2 weeks with or without intravenous bevacizumab or cetuximab). Patients and investigators were not masked to treatment assignment. The primary endpoints were progression-free survival (previously reported) and overall survival (data to be reported at the time of the final analysis). HRQOL outcomes were evaluated as prespecified exploratory endpoints. The analysis population comprised all randomly assigned patients who received at least one dose of study treatment and completed at least one HRQOL assessment. HRQOL outcomes were mean change from baseline to prespecified week 18 in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scale and item scores, and in the EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) visual analogue scale and health utility scores; the proportion of patients with improved, stable, or deteriorated scores from baseline to prespecified week 18 in EORTC QLQ-C30 scales and items; and time to deterioration in EORTC QLQ-C30 global health status/quality of life (GHS/QOL), physical functioning, social functioning, and fatigue scores and EORTC QLQ-CR29 urinary incontinence scores. The threshold for a small and clinically meaningful mean difference in EORTC QLQ-C30 score was 5-8 points. This study is registered with ClinicalTrials.gov, NCT02563002 and is ongoing; recruitment is closed.Between Feb 11, 2016, and Feb 19, 2018, 307 patients were enrolled and randomly assigned to receive pembrolizumab (n=153) or chemotherapy (n=154). The HRQOL analysis population comprised 294 patients (152 receiving pembrolizumab and 142 receiving chemotherapy). As of Feb 19, 2020, median time from randomisation to data cutoff was 32·4 months (IQR 27·7-37·8). Least squares mean (LSM) change from baseline to prespecified week 18 showed a clinically meaningful improvement in EORTC QLQ-C30 GHS/QOL scores with pembrolizumab versus chemotherapy (between-group LSM difference 8·96 [95% CI 4·24-13·69]; two-sided nominal p=0·0002). Median time to deterioration was longer with pembrolizumab versus chemotherapy for GHS/QOL (hazard ratio 0·61 [95% CI 0·38-0·98]; one-sided nominal p=0·019), physical functioning (0·50 [95% CI 0·32-0·81]; one-sided nominal p=0·0016), social functioning (0·53 [95% CI 0·32-0·87]; one-sided nominal p=0·0050), and fatigue scores (0·48 [95% CI 0·33-0·69]; one-sided nominal p<0·0001).Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support pembrolizumab as a first-line treatment option for this population.Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.
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
仔仔仔平完成签到,获得积分10
刚刚
1秒前
2秒前
自信安南完成签到,获得积分10
2秒前
GIANTim完成签到,获得积分10
2秒前
抹茶牛奶配布丁完成签到 ,获得积分10
2秒前
二十八画生完成签到 ,获得积分10
2秒前
1b关闭了1b文献求助
3秒前
3秒前
无医发布了新的文献求助10
3秒前
4秒前
orixero应助缓慢修杰采纳,获得10
4秒前
SCIAI应助bpg28采纳,获得10
4秒前
4秒前
4秒前
刘思琪完成签到,获得积分10
5秒前
zhang狗子完成签到,获得积分20
6秒前
ChenYI发布了新的文献求助10
6秒前
6秒前
wowo完成签到,获得积分10
7秒前
nunu发布了新的文献求助10
7秒前
7秒前
8秒前
Chara0521发布了新的文献求助10
8秒前
胡航航发布了新的文献求助10
8秒前
传奇3应助专注的明轩采纳,获得10
9秒前
zhang狗子发布了新的文献求助10
9秒前
9秒前
9秒前
9秒前
俎树同发布了新的文献求助10
9秒前
慎二完成签到,获得积分10
10秒前
科研通AI2S应助lqkcqmu采纳,获得10
10秒前
zhuan发布了新的文献求助10
11秒前
11秒前
dazzlejj完成签到 ,获得积分10
11秒前
12秒前
下完雨完成签到,获得积分10
12秒前
Minguk发布了新的文献求助10
13秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
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 3970287
求助须知:如何正确求助?哪些是违规求助? 3515034
关于积分的说明 11176923
捐赠科研通 3250301
什么是DOI,文献DOI怎么找? 1795244
邀请新用户注册赠送积分活动 875732
科研通“疑难数据库(出版商)”最低求助积分说明 805039