Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial

催眠药 医学 卡培他滨 临床终点 内科学 安慰剂 肿瘤科 临床研究阶段 腺癌 癌症 胃肠病学 临床试验 化疗 病理 结直肠癌 替代医学
作者
Charles S. Fuchs,Kohei Shitara,Maria Di Bartolomeo,Sara Lonardi,Salah‐Eddin Al‐Batran,Éric Van Cutsem,David H. Ilson,María Alsina,Ian Chau,Jill Lacy,Michel Ducreux,Guillermo Méndez,Alejandro Molina Alavez,Daisuke Takahari,Wasat Mansoor,Peter C. Enzinger,Vera Gorbounova,Zev A. Wainberg,Susanna Hegewisch‐Becker,David Ferry,Ji Lin,Roberto Carlesi,Mayukh Das,Manish A. Shah,A. Luft,Nina Karaseva,Rubén Dario Kowalyszyn,Carlos Alberto San Gil Hernández,Tibor Csõszi,Ferdinando De Vita,Per Pfeiffer,Naotoshi Sugimoto,Judit Kocsis,Andràs Csilla,G. Bodoky,Georgina Garnica Jaliffe,Светлана Проценко,Ayman Madi,Elżbieta Wójcik,Baruch Brenner,Gunnar Folprecht,Tomasz Sarosiek,Katriina Peltola,Peter Bono,Ayala Hubert,Giuseppe Aprile,Cardellino Giovanni Gerardo,Fidel David Huitzil Melendez,Alfredo Falcone,Francesco Di Costanzo,M. Tehfe,Laurent Mineur,Pilar Alfonso,Radka Obermannová,Hélène Senellart,Russell Petty,Leslie Samuel,Péter Ács,Maen Hussein,M. Nechaeva,Frans Erdkamp,Elizabeth Won,Johanna C. Bendell,Javier Gallego Plazas,Sylvie Lorenzen,Bohuslav Melichar,Miguel Angel Escudero,Denis Pezet,Jean-Marc Phélip,Diego Kaen,James A. Reeves,Federico Longo Muñoz,Srinivasan Madhusudan,Carlo Barone,Luis Fein,Ángel Gómez Villanueva,Mohamed Hebbar,Jana Prausová,L. Visa Turmo,J. Vidal Barrull,Mette Yilmaz,Alex Beny,Hanneke W. M. van Laarhoven,Brian DiCarlo,Taito Esaki,Kazumasa Fujitani,Karen Geboes,Ravit Geva,Shigenori Kadowaki,Stephen Leong,Nozomu Machida,Moses S. Raj,Francisco Javier Ramirez Godinez,Ágnes Ruzsa,Hugo Ford,W Lawler,Nicolas Robert Maisey,Jiřı́ Petera,Einat Shacham‐Shmueli,Isabelle Sinapi,Kensei Yamaguchi,Hiroki Hara,J. Thaddeus Beck,Maria Błasińska-Morawiec,Ricardo Villalobos Valencia,Thierry Alcindor,Madhuri Bajaj,Scott Berry,Christina M. Gomez,Daniel Dammrich,Ravindranath Patel,Julien Taieb,Albert J. ten Tije,Ronald L. Burkes,Fernando Cabanillas,Irfan Firdaus,Cynthia C. Chua,Shuichi Hironaka,Ralf‐Dieter Hofheinz,Howard John Lim,Marianne Nordsmark,Béla Pikó,Udit Verma,Jonathan Wadsley,Seigo Yukisawa,Francisco Gutiérrez Delgado,Crystal S. Denlinger,Raija Kallio,Joanna Pikiel,Joanna Wójcik-Tomaszewska,Christine Brezden-Masley,Raymond Woo-Jun Jang,J. Přibylová,Daisuke Sakai,Maria Alejandra Bartoli,Annemieke Cats,M.I. Grootscholten,RA Dichmann,Hugo Hool,Walid Labib Shaib,Akihito Tsuji,Marc Van den Eynde,Hector Velez-Cortez,Timothy R. Asmis
出处
期刊:Lancet Oncology [Elsevier]
卷期号:20 (3): 420-435 被引量:193
标识
DOI:10.1016/s1470-2045(18)30791-5
摘要

VEGF and VEGF receptor 2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether the addition of ramucirumab, a VEGFR-2 antagonist monoclonal antibody, to first-line chemotherapy improves outcomes in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma.For this double-blind, randomised, placebo-controlled, phase 3 trial done at 126 centres in 20 countries, we recruited patients aged 18 years or older with metastatic, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. Eligible patients were randomly assigned (1:1) with an interactive web response system to receive cisplatin (80 mg/m2, on the first day) plus capecitabine (1000 mg/m2, twice daily for 14 days), every 21 days, and either ramucirumab (8 mg/kg) or placebo on days 1 and 8, every 21 days. 5-Fluorouracil (800 mg/m2 intravenous infusion on days 1-5) was permitted in patients unable to take capecitabine. The primary endpoint was investigator-assessed progression-free survival, analysed by intention to treat in the first 508 patients. We did a sensitivity analysis of the primary endpoint, including a central review of CT scans. Overall survival was a key secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT02314117.Between Jan 28, 2015, and Sept 16, 2016, 645 patients were randomly assigned to receive ramucirumab plus fluoropyrimidine and cisplatin (n=326) or placebo plus fluoropyrimidine and cisplatin (n=319). Investigator-assessed progression-free survival was significantly longer in the ramucirumab group than the placebo group (hazard ratio [HR] 0·753, 95% CI 0·607-0·935, p=0·0106; median progression-free survival 5·7 months [5·5-6·5] vs 5·4 months [4·5-5·7]). A sensitivity analysis based on central independent review of the radiological images did not corroborate the investigator-assessed difference in progression-free survival (HR 0·961, 95% CI 0·768-1·203, p=0·74). There was no difference in overall survival between groups (0·962, 0·801-1·156, p=0·6757; median overall survival 11·2 months [9·9-11·9] in the ramucirumab group vs 10·7 months [9·5-11·9] in the placebo group). The most common grade 3-4 adverse events were neutropenia (85 [26%] of 323 patients in the ramucirumab group vs 85 [27%] of 315 in the placebo group), anaemia (39 [12%] vs 44 [14%]), and hypertension (32 [10%] vs 5 [2%]). The incidence of any-grade serious adverse events was 160 (50%) of 323 patients in the ramucirumab group and 149 (47%) of 315 patients in the placebo group. The most common serious adverse events were vomiting (14 [4%] in the ramucirumab group vs 21 [7%] in the placebo group) and diarrhoea (11 [3%] vs 19 [6%]). There were seven deaths in each group, either during study treatment or within 30 days of discontinuing study treatment, which were the result of treatment-related adverse events. In the ramucirumab group, these adverse events were acute kidney injury, cardiac arrest, gastric haemorrhage, peritonitis, pneumothorax, septic shock, and sudden death (n=1 of each). In the placebo group, these adverse events were cerebrovascular accident (n=1), multiple organ dysfunction syndrome (n=2), pulmonary embolism (n=2), sepsis (n=1), and small intestine perforation (n=1).Although the primary analysis for progression-free survival was statistically significant, this outcome was not confirmed in a sensitivity analysis of progression-free survival by central independent review, and did not improve overall survival. Therefore, the addition of ramucirumab to cisplatin plus fluoropyrimidine chemotherapy is not recommended as first-line treatment for this patient population.Eli Lilly and Company.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
楼萌黑完成签到,获得积分10
1秒前
Orange应助碧蓝书易采纳,获得10
2秒前
小橘发布了新的文献求助10
2秒前
轻松的觅露应助kek采纳,获得10
3秒前
liu发布了新的文献求助10
3秒前
下雨天最讨厌了完成签到,获得积分10
3秒前
遇见无铭发布了新的文献求助10
5秒前
一把白刀完成签到 ,获得积分10
5秒前
5秒前
等效边界完成签到,获得积分10
6秒前
6秒前
小二郎应助科研通管家采纳,获得10
6秒前
科研通AI2S应助科研通管家采纳,获得10
6秒前
ikssu应助科研通管家采纳,获得10
6秒前
6秒前
情怀应助科研通管家采纳,获得30
6秒前
上官若男应助科研通管家采纳,获得10
6秒前
无花果应助科研通管家采纳,获得10
7秒前
科研通AI2S应助科研通管家采纳,获得10
7秒前
CodeCraft应助科研通管家采纳,获得30
7秒前
慕青应助科研通管家采纳,获得10
7秒前
beigu应助科研通管家采纳,获得10
7秒前
无花果应助科研通管家采纳,获得10
7秒前
科研通AI2S应助科研通管家采纳,获得10
7秒前
英姑应助科研通管家采纳,获得10
7秒前
科研通AI2S应助科研通管家采纳,获得10
7秒前
7秒前
orixero应助科研通管家采纳,获得10
7秒前
老王完成签到,获得积分10
7秒前
Akim应助科研通管家采纳,获得30
7秒前
大模型应助九月采纳,获得10
9秒前
9秒前
zzw发布了新的文献求助10
11秒前
星辰大海应助陈天明采纳,获得10
12秒前
硕果累累完成签到 ,获得积分10
12秒前
GT完成签到,获得积分10
14秒前
aero发布了新的文献求助10
15秒前
领导范儿应助kk采纳,获得10
15秒前
Qiao完成签到 ,获得积分10
16秒前
慈祥的林完成签到,获得积分10
16秒前
高分求助中
Sustainable Land Management: Strategies to Cope with the Marginalisation of Agriculture 1000
Corrosion and Oxygen Control 600
Python Programming for Linguistics and Digital Humanities: Applications for Text-Focused Fields 500
Heterocyclic Stilbene and Bibenzyl Derivatives in Liverworts: Distribution, Structures, Total Synthesis and Biological Activity 500
重庆市新能源汽车产业大数据招商指南(两链两图两池两库两平台两清单两报告) 400
Division and square root. Digit-recurrence algorithms and implementations 400
行動データの計算論モデリング 強化学習モデルを例として 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 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 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2546683
求助须知:如何正确求助?哪些是违规求助? 2175850
关于积分的说明 5601387
捐赠科研通 1896684
什么是DOI,文献DOI怎么找? 946382
版权声明 565379
科研通“疑难数据库(出版商)”最低求助积分说明 503569