ONCOLOGYEDUCATION.COM ARTICLE SUMMARIES 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 Wilke, H., et al., Lancet, doi: 10.1016/S1470-2045(14)70420-6

BACKGROUND Ramucirumab is a novel VEGFR-2 receptor antibody that improves OS in gastric cancer when used as monotherapy in the 2nd line (REGARD trial, previously reviewed by OncologyEducation.com) The RAINBOW study examines ramucirumab in combination with taxane. Wilke, H., et al., Lancet, doi: 10.1016/S1470-2045(14)70420-6

*platinum plus fluoropyrimidine with or without an anthracycline STUDY DESIGN Primary Outcome: OS N = 665 Ramucirumab (8 mg/kg IV on days 1 &15) + Paclitaxel (80 mg/m2 IV on days 1, 8, & 15) 28 day cycle Patients with advanced gastric or gastro-esophageal junction adenocarcinoma with disease progression after/within 4 months of 1st Line chemotherapy* Placebo + Paclitaxel *platinum plus fluoropyrimidine with or without an anthracycline Wilke, H., et al., Lancet, doi: 10.1016/S1470-2045(14)70420-6

Ramucirumab + Paclitaxel RESULTS - EFFICACY Ramucirumab + Paclitaxel Placebo + Paclitaxel Hazard Ratio p-Value OS 9.6 mo 7.4 mo 0.807 (0.678-0.962) 0.0017 PFS 4.4 mo 2.9 mo 0.635 (0.536-0.752) p < 0.0001 ORR 28% 16% 0.0001 Wilke, H., et al., Lancet, doi: 10.1016/S1470-2045(14)70420-6

RESULTS – SAFETY and QOL Ramucirumab + Paclitaxel Placebo + Paclitaxel Grade III/IV Neutropenia 41% 19% Grade III/IV Leucopenia 17% 7% Grade III/IV Hypertension 14% 2% Grade III/IV Fatigue 12% 5% Grade III/IV Anaemia 9% 10% Grade III/IV Abdominal Pain 6% 3% Grade III/IV Febrile Neutropenia Wilke, H., et al., Lancet, doi: 10.1016/S1470-2045(14)70420-6

SUMMARY The RAINBOW trial has shown that the addition of ramucirumab to weekly paclitaxel produces a modest improvement in OS. Wilke, H., et al., Lancet, doi: 10.1016/S1470-2045(14)70420-6

COMMENTARY Clinicians will need to discuss with their patients whether the modest benefit (OS difference 2.2m, HR 0.8) observed justifies ramucirumab’s increased toxicity. Wilke, H., et al., Lancet, doi: 10.1016/S1470-2045(14)70420-6