696P - A multi-center phase II study and predictive biomarker analysis of combined cetuximab and modified FOLFIRI as second-line treatment in patients with...
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation II|
|Topics|| Gastric Cancer
This study was conducted to explore potential biomarkers for predicting clinical outcome of cetuximab in combination with modified FOLFIRI (mFOLFIRI) and to analyze safety of this regimen as a second-line treatment in metastatic gastric cancer patients.Methods
A total of 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m2) and weekly doses (250 mg/m2) thereafter. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m2), leucovorin (200 mg/m2), and an IV bolus dose of 5-FU (400 mg/m2) followed by a continuous infusion of 5-FU (2400 mg/m2) for 46 hours. The primary endpoint was time-to-progression (TTP).Findings
The response rate (RR) was 33.3% among 54 evaluable patients. In the intention-to-treat (ITT) 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). It was demonstrated that plasma vascular endothelial growth factor (VEGF) levels could be a predictive factor for the treatment prognosis. 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.Interpretation
Low baseline plasma VEGF levels were identified as a potential predictive biomarker of prognosis. Combination therapy comprising cetuximab and mFOLFIRI was well tolerated, which would be potentially used as a second-line treatment for patients with advanced gastric cancer.Funding
This study was supported by Fudan University Shanghai Cancer Center; Merck KGaA Darmstadt, Germany, and National “Eleventh Five-year plan” new drug discovery major projects of P. R. China.Disclosure
All authors have declared no conflicts of interest.