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Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial

 Charles S Fuchs  ;  Jiri Tomasek  ;  Cho Jae Yong  ;  Filip Dumitru  ;  Rodolfo Passalacqua  ;  Chanchal Goswami  ;  Howard Safran  ;  Lucas Vieira dos Santos  ;  Giuseppe Aprile  ;  David R Ferry  ;  Bohuslav Melichar  ;  Mustapha Tehfe  ;  Eldar Topuzov  ;  John Raymond Zalcberg  ;  Ian Chau  ;  William Campbell  ;  Choondal Sivanandan  ;  Joanna Pikiel  ;  Minori Koshiji  ;  Yanzhi Hsu  ;  Astra M Liepa  ;  Ling Gao  ;  Jonathan D Schwartz 
 LANCET, Vol.383(9911) : 31-39, 2014 
Journal Title
Issue Date
Adenocarcinoma/drug therapy* ; Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Disease Progression ; Double-Blind Method ; Esophageal Neoplasms/drug therapy ; Esophagogastric Junction* ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Quality of Life ; Stomach Neoplasms/drug therapy* ; Treatment Outcome ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; Young Adult
Vascular endothelial growth factor (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 ramucirumab, a monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with advanced gastric cancer.
We did an international, randomised, double-blind, placebo-controlled, phase 3 trial between Oct 6, 2009, and Jan 26, 2012, at 119 centres in 29 countries in North America, Central and South America, Europe, Asia, Australia, and Africa. Patients aged 24-87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were randomly assigned (2:1), via a central interactive voice-response system, to receive best supportive care plus either ramucirumab 8 mg/kg or placebo, intravenously once every 2 weeks. The study sponsor, participants, and investigators were masked to treatment assignment. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00917384.
355 patients were assigned to receive ramucirumab (n=238) or placebo (n=117). Median overall survival was 5·2 months (IQR 2·3-9·9) in patients in the ramucirumab group and 3·8 months (1·7-7·1) in those in the placebo group (hazard ratio [HR] 0·776, 95% CI 0·603-0·998; p=0·047). The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors (multivariable HR 0·774, 0·605-0·991; p=0·042). Rates of hypertension were higher in the ramucirumab group than in the placebo group (38 [16%] vs nine [8%]), whereas rates of other adverse events were mostly similar between groups (223 [94%] vs 101 [88%]). Five (2%) deaths in the ramucirumab group and two (2%) in the placebo group were considered to be related to study drug.
Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy. Our findings validate VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer.
ImClone Systems.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Jae Yong(조재용) ORCID logo https://orcid.org/0000-0002-0926-1819
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