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Lancet Oncol. 2014 Oct;15(11):1224-35. doi: 10.1016/S1470-2045(14)70420-6. Epub 2014 Sep 17.

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.

Author information

1
Department of Medical Oncology/Haematology, Kliniken Essen-Mitte, Germany. Electronic address: h.wilke@kliniken-essen-mitte.de.
2
Aichi Cancer Center Hospital, Japan.
3
University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven, Belgium.
4
Korea University Guro Hospital, Seoul, South Korea.
5
St László Hospital, Department of Oncology, Budapest Gastrointestinal Medical Oncology, Budapest, Hungary.
6
National Cancer Center Hospital, Tokyo, Japan.
7
Clinical Trial Promotion Department, Chiba Cancer Center, Japan.
8
Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
9
Republican Clinical Oncology Dispensary, Ufa, Russia.
10
Seoul National University Cancer Hospital, Seoul, South Korea.
11
Royal Marsden Hospital, London, UK.
12
Centre Hospitalier Universitaire Georges Pompidou Assistance Publique-Hôpitaux de Paris, Université Paris V, France.
13
Hokkaido University Hospital Cancer Center, Japan.
14
University of Texas M D Anderson Cancer Center, Houston, TX, USA.
15
Eli Lilly Deutschland, Bad Hamburg, Germany.
16
Eli Lilly Italia, Sesto Fiorentino, Italy.
17
New Cross Hospital, Wolverhampton, UK.
18
Eli Lilly and Company, Bridgewater, NJ, USA.
19
Stemline Therapeutics, New York, NY, USA.
20
Gastrointestinal, Oncology, National Cancer Center Hospital East, Japan.

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.

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.

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%]).

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.

FUNDING:

Eli Lilly and Company.

PMID:
25240821
DOI:
10.1016/S1470-2045(14)70420-6
[Indexed for MEDLINE]

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