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Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.
- Source :
-
The Lancet. Oncology [Lancet Oncol] 2014 Oct; Vol. 15 (11), pp. 1224-35. Date of Electronic Publication: 2014 Sep 17. - Publication Year :
- 2014
-
Abstract
- Background: VEGFR-2 has a role in gastric cancer pathogenesis and progression. We assessed whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel.<br />Methods: This randomised, placebo-controlled, double-blind, phase 3 trial was done at 170 centres in 27 countries in North and South America, Europe, Asia, and Australia. Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy (platinum plus fluoropyrimidine with or without an anthracycline) were randomly assigned with a centralised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15, plus paclitaxel 80 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle. A permuted block randomisation, stratified by geographic region, time to progression on first-line therapy, and disease measurability, was used. The primary endpoint was overall survival. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one treatment with study drug. This trial is registered with ClinicalTrials.gov, number NCT01170663, and has been completed; patients who are still receiving treatment are in the extension phase.<br />Findings: Between Dec 23, 2010, and Sept 23, 2012, 665 patients were randomly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel. Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group (median 9·6 months [95% CI 8·5-10·8] vs 7·4 months [95% CI 6·3-8·4], hazard ratio 0·807 [95% CI 0·678-0·962]; p=0·017). Grade 3 or higher adverse events that occurred in more than 5% of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia (133 [41%] of 327 vs 62 [19%] of 329), leucopenia (57 [17%] vs 22 [7%]), hypertension (46 [14%] vs eight [2%]), fatigue (39 [12%] vs 18 [5%]), anaemia (30 [9%] vs 34 [10%]), and abdominal pain (20 [6%] vs 11 [3%]). The incidence of grade 3 or higher febrile neutropenia was low in both groups (ten [3%] vs eight [2%]).<br />Interpretation: The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel, and could be regarded as a new standard second-line treatment for patients with advanced gastric cancer.<br />Funding: Eli Lilly and Company.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adenocarcinoma mortality
Adenocarcinoma pathology
Adult
Aged
Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal adverse effects
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols adverse effects
Confidence Intervals
Disease-Free Survival
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Esophageal Neoplasms mortality
Esophageal Neoplasms pathology
Esophagogastric Junction pathology
Female
Humans
Kaplan-Meier Estimate
Male
Maximum Tolerated Dose
Middle Aged
Paclitaxel administration & dosage
Paclitaxel adverse effects
Prognosis
Proportional Hazards Models
Stomach Neoplasms mortality
Stomach Neoplasms pathology
Survival Analysis
Treatment Outcome
Ramucirumab
Adenocarcinoma drug therapy
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Esophageal Neoplasms drug therapy
Remission Induction methods
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1474-5488
- Volume :
- 15
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Lancet. Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 25240821
- Full Text :
- https://doi.org/10.1016/S1470-2045(14)70420-6