Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial

医学 打开标签 彭布罗利珠单抗 间皮瘤 内科学 化疗 随机对照试验 肿瘤科 癌症 病理 免疫疗法
作者
Quincy Chu,Federica Perrone,Laurent Greillier,Wei Tu,Maria Carmela Piccirillo,Federica Grosso,Giuseppe Lo Russo,Marie Florescu,Manlio Mencoboni,Alessandro Morabito,Fabiana Letizia Cecere,Giovanni Luca Ceresoli,David E. Dawe,Paolo Andrea Zucali,Maria Pagano,John R. Goffin,Myriam Locatelli Sanchez,Cesare Gridelli,Gérard Zalcman,Xavier Quantin
出处
期刊:The Lancet [Elsevier BV]
卷期号:402 (10419): 2295-2306 被引量:42
标识
DOI:10.1016/s0140-6736(23)01613-6
摘要

Summary

Background

Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum–pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum–pemetrexed would improve overall survival in patients with pleural mesothelioma.

Methods

We did this open-label, international, randomised phase 3 trial at 51 hospitals in Canada, Italy, and France. Eligible participants were aged 18 years or older, with previously untreated advanced pleural mesothelioma, with an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) to intravenous chemotherapy (cisplatin [75 mg/m2] or carboplatin [area under the concentration-time curve 5–6 mg/mL per min] with pemetrexed 500 mg/m2, every 3 weeks for up to 6 cycles), with or without intravenous pembrolizumab 200 mg every 3 weeks (up to 2 years). The primary endpoint was overall survival in all randomly assigned patients; safety was assessed in all randomly assigned patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02784171, and is closed to accrual.

Findings

Between Jan 31, 2017, and Sept 4, 2020, 440 patients were enrolled and randomly assigned to chemotherapy alone (n=218) or chemotherapy with pembrolizumab (n=222). 333 (76 %) of patients were male, 347 (79%) were White, and median age was 71 years (IQR 66–75). At final analysis (database lock Dec 15, 2022), with a median follow-up of 16·2 months (IQR 8·3–27·8), overall survival was significantly longer with pembrolizumab (median overall survival 17·3 months [95% CI 14·4–21·3] with pembrolizumab vs 16·1 months [13·1–18·2] with chemotherapy alone, hazard ratio for death 0·79; 95% CI 0·64–0·98, two-sided p=0·0324). 3-year overall survival rate was 25% (95% CI 20–33%) with pembrolizumab and 17% (13–24%) with chemotherapy alone. Adverse events related to study treatment of grade 3 or 4 occurred in 60 (27%) of 222 patients in the pembrolizumab group and 32 (15%) of 211 patients in the chemotherapy alone group. Hospital admissions for serious adverse events related to one or more study drugs were reported in 40 (18%) of 222 patients in the pembrolizumab group and 12 (6%) of 211 patients in the chemotherapy alone group. Grade 5 adverse events related to one or more drugs occurred in two patients on the pembrolizumab group and one patient in the chemotherapy alone group.

Interpretation

In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum–pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival. This regimen is a new treatment option for previously untreated advanced pleural mesothelioma.

Funding

The Canadian Cancer Society and Merck & Co.
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
思源应助17712570999采纳,获得10
刚刚
刚刚
汉堡包应助乐情采纳,获得10
3秒前
LLANN发布了新的文献求助10
3秒前
zzx发布了新的文献求助10
3秒前
4秒前
Akim应助菲菲采纳,获得10
4秒前
Kuma完成签到,获得积分10
4秒前
踏实口红完成签到,获得积分10
4秒前
子车雁开完成签到,获得积分10
5秒前
Hannah发布了新的文献求助10
5秒前
5秒前
乐正亦寒发布了新的文献求助50
6秒前
6秒前
www完成签到,获得积分10
7秒前
7秒前
青石发布了新的文献求助10
10秒前
竹焚完成签到 ,获得积分10
12秒前
俞若枫发布了新的文献求助30
12秒前
汉堡包应助zzx采纳,获得10
14秒前
yan完成签到,获得积分10
14秒前
15秒前
15秒前
英姑应助Cecilia采纳,获得10
16秒前
jianglu完成签到,获得积分10
16秒前
风姿物语完成签到,获得积分10
17秒前
18秒前
wanci应助Sj泽采纳,获得10
18秒前
19秒前
20秒前
17712570999完成签到,获得积分10
20秒前
20秒前
insane完成签到,获得积分10
21秒前
xiao完成签到 ,获得积分10
21秒前
22秒前
扶桑发布了新的文献求助10
22秒前
insane发布了新的文献求助10
23秒前
随影相伴完成签到 ,获得积分10
24秒前
mitty发布了新的文献求助10
24秒前
26秒前
高分求助中
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Effective Learning and Mental Wellbeing 300
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 3975250
求助须知:如何正确求助?哪些是违规求助? 3519625
关于积分的说明 11199055
捐赠科研通 3255962
什么是DOI,文献DOI怎么找? 1798001
邀请新用户注册赠送积分活动 877358
科研通“疑难数据库(出版商)”最低求助积分说明 806298