| General information |
| Database: | DB00458 |
| Objective: | They aimed to assess whether ramucirumab, a monoclonal antibody VEGFR2 antagonist, prolonged survival in patients with advanced gastric cancer. |
| Authors: | Fuchs CS, et al |
| Title: | Ramucirumab monotherapy for previously treated advanced gastric or gastrooesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebocontrolled, phase 3 trial. |
| Journal: | Lancet. |
| Year: | 2014 |
| PMID: | 24094768 |
| Trial Design |
| Clinical Trial Id: | NCT00917384 |
| Agent: | ramucirumab
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced adenocarcinoma of the stomach or gastroesophageal junction |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | international, randomised, doubleblind, placebocontrolled, phase III trial |
| Key Patients Feature: | Eligible patients aged 24-87 years hadmetastatic or unresectable, locally recurrent gastric orgastrooesophageal junction adenocarcinoma; had haddisease progression within 4 months of the last dose offirstline platinumcontaining or fluoropyrimidinecontaining chemo therapy for metastatic disease, or within6 months of the last dose of platinumcontaining orfluoropyrimidinecontaining adjuvant treatment; andhad an Eastern Cooperative Oncology Group (ECOG)performance status score of 0 or 1. they included patientswith measurable disease (defined by Response EvaluationCrieria In Solid Tumours [RECIST] version 1.0)15 orevaluable disease. Major exclusion criteria included anygrade 3 or higher gastrointestinal bleeding (defined byNational Cancer Institute Common Terminology Criteriafor Adverse Events [NCICTCAE], version 4.02)16 within3 months before randomisation; any arterial thromboembolic event, including myocardial infarction, unstableangina, transient ischaemic event, cerebrovascular accident within 6 months before random isation; or poorlycontrolled hypertension. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Ramucirumab VS Placebo |
| Treatment Info: | pts were randomly assigned (2:1), via a central interactive voiceresponse system, to receive best supportive care plus either ramucirumab 8 mg/kg or placebo, intravenously once every 2 weeks. |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 355 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | in Ramucirumab group(n=238), Complete response < 1%, Partial response 3%, Stable disease 45%, Progressive disease 33%, Objective response 3%, Disease control rate 49%.in Placebo group (n=117), Complete response 0, Partial response 3%, Stable disease 21%, Progressive disease 54%, Objective response 3%, Disease control rate 23% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.1 months (IQR 1.3-4.2) in patients receiving ramucirumab and 1.3 months (1.1-2.1) in those receiving placebo. |
| Median OS A vs. C: | 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). |
| Adverse Event(agent arm): | 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. |
| Conclusions: | Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastrooesophageal junction adenocarcinoma progressing after firstline chemotherapy. Our findings validate VEGFR2 signalling as an important therapeutic target in advanced gastric cancer. |