• Gastrointestinal Cancers Clinical Trials

• Gastrointestinal Cancers Clinical Trials

The Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma [RAINBOW; NCT01170663] is an international double-blind Phase 3 study of patients with metastatic gastric or gastroesophageal junction adenocarcinoma. Eligible patients were those with disease progression within 4 months after receiving first-line platinum- and fluoropyrimidine-based combination chemotherapy, ECOG Performance Status ≤ 1, and adequate organ function. Patients were randomized to treatment with paclitaxel (PTX), 80 mg/m², on Days 1, 8, and 15 of a 4-week cycle, combined with either the human immunoglobulin 1 vascular endothelial growth factor receptor 2 targeted antibody ramucirumab (RAM), 8 mg/kg, given intravenously Q2W, or placebo. Randomization was stratified by region, the time to progression after the initial dose of first-line therapy (< 6 vs ≥ 6 months), and whether or not the disease was measurable. Hansjochen Wilke, MD, Kliniken Essen-Mitte, Essen, Germany, presented the results from the planned region 1 subgroup analysis [Wilke H et al. Ann Oncol. 2014 (abstr O-0006)]. Region 1 consisted of Europe, Israel, the United States, and Australia; region 2 included Argentina, Brazil, Chile, and Mexico; and Japan, South Korea, Hong Kong, Singapore, and Taiwan made up region 3.

After randomization, patients received treatment and were monitored until disease progression, toxicity requiring study drug discontinuation, protocol noncompliance, or withdrawal of consent. Overall survival (OS) was the primary end point. Progression-free survival (PFS), objective response rate (ORR), time to progression (TTP), and safety were the secondary end points. A stratified log-rank test was used to compare OS and PFS between treatment groups. The ORR was calculated with a Cochran-Mantel-Haenszel test.

A total of 665 patients were randomized worldwide from December 2010 to September 2012 [Wilke H et al. Ann Oncol. 2014 (abstr O-0006); J Clin Oncol. 2014 (abstr LBA7)]. Of these, 398 were from region 1: 198 in the RAM + PTX group and 200 receiving PTX alone. The baseline characteristics of the patients were considered well balanced between the 2 treatment groups. The median OS was 8.57 months for patients in the RAM + PTX group and 5.91 months for patients receiving PTX alone (HR, 0.726; 95% CI, 0.580 to 0.909; p = .0050). Median PFS was 4.24 months for RAM + PTX versus 2.83 months for PTX alone (HR, 0.631; 95% CI, 0.506 to 0.786; p < .0001). The median TTP was 5.36 months for the RAM + PTX group, compared with 3.15 months for PTX alone (p = .0002). The ORR was 26.8% for patients receiving RAM + PTX and 13.0% in the PTX arm (p = .0004). The significant benefits observed in the Western population were consistent with those observed in the overall intent-to-treat population.

The adverse event profile of the region 1 subgroup was also considered similar to that of the overall patient population. Adverse events grade 3 or higher that occurred in > 5% of patients receiving RAM + PTX were neutropenia (32.1% [RAM + PTX] vs 14.7% [PTX]), 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% in both treatment arms).

These results demonstrate that in the Western population, just as in the overall study population, the combination of RAM and PTX resulted in better survival parameters at the expense of significantly increased risk for neutropenia.

• © 2014 MD Conference Express®