A multi-center phase II study and biomarker analysis of combined cetuximab and modified FOLFIRI as second-line treatment in patients with metastatic gastric cancer

BACKGROUND: To evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes. METHODS: All 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m(2)) and weekly doses (250 mg/m(2)) thereafter, starting on day 1. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m(2)), leucovorin (200 mg/m(2)), and an IV bolus dose of 5-FU (400 mg/m(2)) followed by a continuous infusion of 5-FU (2400 mg/m(2)) for 46 h. The primary endpoint was time-to-progression (TTP). RESULTS: The response rate (RR) was 33.3% among 54 evaluable patients. In the intention-to-treat analysis, median TTP was 4.6 months (95% confidential interval [CI]: 3.6-5.6 months) and median overall survival (OS) was 8.6 months (95% CI: 7.3-9.9 months). In univariate analyses, plasma vascular endothelial growth factor (VEGF) levels were correlated with clinical outcome. In patients with low (≤12.6 pg/ml) and high (>12.6 pg/ml) baseline plasma VEGF levels, RR values were 55.0% and 5.3%, respectively (P = 0.001); median TTP values were 6.9 months and 2.8 months, respectively (P = 0.0005); and median OS values were 12 months and 5 months, respectively (P <0.0001). None of these patients exhibited KRAS, BRAF, or PIK3CA mutations. CONCLUSIONS: Combination therapy comprising cetuximab and mFOLFIRI was well tolerated and active as a second-line treatment for patients with metastatic gastric cancer. Patients with low baseline plasma VEGF levels were associated with better clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov. NCT00699881. Registered 17 June 2008 (retrospectively registered)