RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE).

Cancers of the Esophagus and Stomach
Session Type and Session Title: 
General Poster Session A: Cancers of the Esophagus and Stomach
Oral Abstract Session: Cancers of the Esophagus and Stomach (eQ&A)
Abstract Number: 
J Clin Oncol 32, 2014 (suppl 3; abstr LBA7)
Hansjochen Wilke, Eric Van Cutsem, Sang Cheul Oh, Gyorgy Bodoky, Yasuhiro Shimada, Shuichi Hironaka, Naotoshi Sugimoto, Oleg N. Lipatov, Tae-You Kim, David Cunningham, Atsushi Ohtsu, Philippe Rougier, Michael Emig, Roberto Carlesi, Kumari Chandrawansa, Kei Muro; Kliniken Essen Mitte Center of Pallative Care, Essen, Germany; Digestive Oncology Unit, Leuven Cancer Institute, Leuven, Belgium; Korea University Guro Hospital, Seoul, South Korea; Szent László Hospital, Budapest, Hungary; Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan; Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan; Department of Clinical Oncology and Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Bashkortostan Clinical Oncology Center, Ufa, Russia; Department of Internal Medicine and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom; National Cancer Center Hospital East, Kashiwa, Japan; Hopital Europeen Georges Pompidou, Université Paris V, France, Paris, France; Eli Lilly and Company, Heidelberg, Germany; Eli Lilly Italia S.p.A., Sesto Fiorentino FL, Italy; Eli Lilly and Company, Bridgewater, NJ; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: RAM is a human IgG1 monoclonal antibody VEGF-receptor 2 antagonist. We conducted a global, placebo-controlled, double-blind, phase III trial to evaluate the efficacy and safety of PTX +/- RAM in patients with metastatic GEJ or gastric adenocarcinoma who had disease progression on or within 4 months after first-line platinum- and fluoropyrimidine-based combination therapy. Methods: Pts received RAM (8 mg/kg IV q2w) or placebo (PL) plus PTX (80 mg/m2 d1, 8, 15 of a 4 week cycle) until disease progression, unacceptable toxicity, or death. Eligible pts had ECOG PS ≤ 1; and adequate organ function. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), time to progression (TTP), and safety. Results: From Dec 2010 to Sep 2012, 665 pts were randomized (RAM+PTX: 330; PTX: 335). Baseline characteristics were generally balanced between arms. The OS hazard ratio (HR) was 0.807 (95% CI 0.678, 0.962; p=0.0169). Median OS was 9.63m for RAM+PTX and 7.36m for PTX. The HR for PFS was 0.635 (95% CI 0.536, 0.752; p <0.0001). Median PFS was 4.40m and 2.86m. Median TTP was 5.5m RAM+PTX; 3.0m PTX (p <0.0001). ORR was 28% RAM+PTX;16% PTX (p=0.0001). Grade ≥ 3 adverse events (AEs) occurring in >5% of patients on RAM+PTX were: neutropenia (40.7% RAM+PTX;18.8% PTX), leukopenia (17.4% vs 6.7% ), hypertension (14.1% vs 2.4%), anemia (9.2% vs 10.3%), fatigue (7.0% vs 4.0%), abdominal pain (5.5% vs 3.3%), and asthenia (5.5% vs 3.3%). Febrile neutropenia was reported in 3.1% RAM+PTX; 2.4% PTX. Conclusions: The primary endpoint of improved OS was met. A statistically significant and clinically meaningful OS benefit of > 2 months was observed for RAM+PTX vs. PTX in gastric and GEJ cancer after progression on 1st-line therapy, as were significant benefits in PFS and ORR. Neutropenia was more frequently reported in the RAM+PTX arm but incidence of febrile neutropenia was comparable between arms. Clinical trial information: NCT01170663.