Eric Van Cutsem, MD, PhD
A geographic analysis of clinical trial results supporting the use of ramucirumab (Cyramza) in advanced gastric cancer demonstrated that patients in the United States and other Western nations experienced similar survival gains and adverse events as did their counterparts in two other regions of the world. Subgroup results from the RAINBOW trial were presented during the ESMO 16th World Congress on Gastrointestinal Cancer.
Eric Van Cutsem, MD, PhD, who co-chaired the congress, presented findings from RAINBOW, a global double-blinded, phase III trial. “The efficacy and safety from Western patients in Region 1 were similar to patients in the overall population,” said Van Cutsem, of the Digestive Oncology Unit at the Leuven Cancer Institute in Belgium. “Ramucirumab plus paclitaxel should be considered the new second-line standard of care for advanced gastric cancer.”
Ramucirumab is a humanized IgG1 monoclonal antibody vascular endothelial growth factor receptor 2 (VEGFR2) antagonist that blocks the binding of VEGF ligands. The FDA approved the intravenously administered agent as monotherapy for patients with advanced gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma after prior fluoropyrimidine- or platinum-containing chemotherapy based upon data from the REGARD trial.2
The RAINBOW trial evaluated the efficacy and safety of paclitaxel with and without ramucirumab in patients with gastric adenocarcinoma or GEJ whose disease progressed during or within 4 months after first-line platinum- and fluoropyrimidine-based combination therapy. Results from an earlier analysis of the trial were submitted to the FDA, with a review pending.
RAINBOW enrolled 665 patients with ECOG PS â‰¤1 and adequate organ function from three areas: Region 1, consisting of the United States, Europe, Israel, and Australia; Region 2, including Mexico, Brazil, Argentina, and Chile; and Region 3, composing Japan, South Korea, Hong Kong, Singapore, and Taiwan.
All patients received paclitaxel at 80 mg/m2
on days 1, 8, 15 of a 4-week cycle; 330 patients were assigned to ramucirumab at 8 mg/kg IV once every 2 weeks (q2w) or placebo (n = 335) until disease progression, unacceptable toxicity, or death.
Van Cutsem compared data from Region 1 patients with findings for participants in the overall population. Region 1 enrolled 398 patients; 198 patients were assigned ramucirumab and 200 received placebo. Baseline characteristics, including baseline tumor characteristics, in the overall population and Region 1 patients were well balanced between treatment arms.
In the overall cohort, RAINBOW met the primary endpoint of overall survival (OS); median OS was 9.6 months for ramucirumab/paclitaxel compared with 7.4 months for placebo/paclitaxel, hazard ratio [HR] = 0.807, 95% CI 0.678-0.962; P
The trial also met the secondary endpoints; median progression-free survival (PFS) was 4.40 months and 2.9 months for ramucirumab and placebo, respectively, HR = 0.635 (P
< .0001). The objective response rate (ORR) was 28% with ramucirumab versus 16% with placebo (P
= .0001). Median time to progression (TTP) was 5.5 months with ramucirumab and 3.0 months with placebo (P
The secondary endpoint of safety was also met; neutropenia was more frequently reported with ramucirumab but the incidence of febrile neutropenia was comparable between arms.
Region 1 results were consistent with the overall findings. The difference in OS between treatment arms was 2.3 months in the overall population (P
= .0169) and 2.7 (P
= .0050) months in Region 1. The difference in PFS between treatment arms was 1.5 months and 1.4 months in the overall and Region 1 populations, respectively, (both differences P
Median OS was 8.6 months for ramucirumab/paclitaxel compared with 5.9 months for placebo/paclitaxel (hazard ratio [HR] = 0.726; 95% CI 0.580-0.909; P
= .005). Median PFS was 4.2 months and 2.8 months for ramucirumab and placebo, respectively, (HR = 0.631; 95% CI 0.506-0.786; P
<.0001). ORR was 26.8% and 13% in the respective arms (P
= .0004). Median TTP was 5.36 months with ramucirumab and 3.15 months with placebo (P
Adverse events of grades 3 or 4 severity occurring in more than 5% of Region 1 patients included 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 deterioration, which occurred in 5.6% of patients in both treatment arms.
Eli Lilly and Company, which developed the drug, supported the study.