Rainbow: A Global, Phase 3, Double-Blind Study of Ramucirumab Plus Paclitaxel Versus Placebo Plus Paclitaxel in the Treatment of Gastric Cancer Following Disease Progression: Western Population Subgroup

Abstract

Introduction: RAINBOW, a global, placebo‐controlled, double‐blind, phase III trial, demonstrated significant improvements in overall survival (OS) (hazard ratio (HR) 0.807; 95% CI 0.678, 0.962; p = 0.0169), progression‐free survival (PFS) (HR 0.635; 95%CI 0.536, 0.752; p < 0.0001), and response rates (ORR 27.9% RAM + PTX;16.1 PTX p= 0.0001) in advanced gastric or GEJ adenocarcinoma patients receiving ramucirumab (RAM), a human IgG1 VEGF receptor 2 targeted antibody, plus paclitaxel (PTX).We present the pre‐planned subgroup analysis of Western patients (Region 1). 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 until other discontinuation criteria were met. Eligible pts had ECOG PS ≤ 1 and adequate organ function. Randomisation was stratified by geographic region (Region 1: Europe (including Israel), Australia, and United States, Region 2: Argentina, Brazil, Chile, and Mexico, and Region 3: Japan, South Korea, Hong Kong, Singapore, and Taiwan), time to progression after first dose of first line therapy (< 6 months vs ≥ 6 months), and disease measurability (measurable vs. nonmeasurable). OS and PFS were compared between treatment arms using a stratified log‐rank test. ORR was analyzed using a CMH test. Results: Of the 665 worldwide patients, 398Western patients (Europe including Israel, US, AUS) were randomized (RAM + PTX: 198; PTX: 200). Baseline characteristics were generally balanced between arms. The OS Hazard Ratio (HR) was 0.726 (95% CI 0.580, 0.909; p = 0.0050). Median OS was 8.57m for RAM + PTX and 5.91m for PTX. The HR for PFS was 0.631 (95% CI 0.506, 0.786; p < 0.0001). Median PFS was 4.24m and 2.83 m. Median TTP was 5.36m RAM + PTX; 3.15m PTX (p = 0.0002). ORR was 26.8% RAM + PTX; 13.0% PTX (p = 0.0004). Grade ≥ 3 adverse events (AEs) occurring in >5% of patients on RAM + PTX were: neutropenia (32.1% vs. 14.7%), hypertension (17.9% vs. 2.0%), leukopenia (9.7% vs. 4.1%), fatigue (10.2% vs. 5.1%), asthenia (7.7% vs. 2.0%), anemia (6.6% vs. 6.1%), abdominal pain (6.6% vs. 4.6%), and general physical health deterioration (5.6% both arms). Conclusion: In the Western population of the RAINBOW study, the significant benefits observed in OS, PFS, and ORR were consistent with those in the overall ITT population. The adverse event profile was similar to the overall population with neutropenia, hypertension, leukopenia and fatigue\asthenia more frequently reported in the RAM + PTX arm.