BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: ImClone Systems.
- MeSH
- adenokarcinom farmakoterapie MeSH
- antitumorózní látky škodlivé účinky terapeutické užití MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- gastroezofageální junkce * MeSH
- humanizované monoklonální protilátky MeSH
- inhibitory angiogeneze terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- monoklonální protilátky škodlivé účinky terapeutické užití MeSH
- nádory jícnu farmakoterapie MeSH
- nádory žaludku farmakoterapie MeSH
- progrese nemoci MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- ramucirumab MeSH
- receptor 2 pro vaskulární endoteliální růstový faktor antagonisté a inhibitory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- antitumorózní látky MeSH
- humanizované monoklonální protilátky MeSH
- inhibitory angiogeneze MeSH
- monoklonální protilátky MeSH
- receptor 2 pro vaskulární endoteliální růstový faktor MeSH
