Format

Send to

Choose Destination
See comment in PubMed Commons below
Lancet. 2014 Jan 4;383(9911):31-9. doi: 10.1016/S0140-6736(13)61719-5. Epub 2013 Oct 3.

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

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: cfuchs@partners.org.
2
Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
3
Department of Medical Oncology, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Korea.
4
Oncology Department, Emergency County Hospital "Dr Constantin Opris", Baia Mare, Romania.
5
Medical Oncology Division, Istituti Ospitalieri di Cremona, Cremona, Italy.
6
Department of Medical Oncology, B P Poddar Hospital and Medical Research, Kolkata, West Bengal.
7
Department of Medicine, The Brown University Oncology Group, Brown University, Providence, RI, USA.
8
Medical Oncology Department, Gastrointestinal Oncology Division, Hospital de Câncer de Barretos and Hemomed Instituto de Oncologia e Hematologia, São Paulo, Brazil.
9
Department of Oncology, University and General Hospital, Udine, Italy.
10
Department of Medical Oncology, New Cross Hospital, West Midlands, UK.
11
Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, CzechRepublic.
12
Department of Medical Oncology, Hôpital Notre Dame de CHUM, Montreal, Quebec.
13
State Budgetary Educational Institution of Higher Professional Education (SBEIHPE), "Northwest State Medical University na II Mechnikov", Ministry of Healthcare of the Russian Federation, Russia.
14
Division of Cancer Medicine, Peter McCallum Cancer Centre, East Melbourne, VIC, Australia; Departments of Medicine and Oncology, Faculty of Medicine, University of Melbourne, Australia.
15
Department of Medicine, Royal Marsden Hospital, London and Surrey, England.
16
Department of Oncology, Hospital Herrera Llerandi-Clinicas Médicas, Guatemala.
17
Division of Cancer Research, Regional Cancer Centre, Kerala, India.
18
Wojewódzkie Centrum Onkologii Gdańsk, Poland.
19
ImClone Systems LLC, Bridgewater, NJ, USA.
20
Eli Lilly, Indianapolis, IN, USA.
21
Medical Oncology Department Vall d'Hebron University Hospital, UniversitatAutònoma de Barcelona, Barcelona, Spain.

Abstract

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.

PMID:
24094768
DOI:
10.1016/S0140-6736(13)61719-5
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center