Irinotecan/Capecitabine (Xeliri) Plus Bevacizumab Versus Irinotecan/Fluorouracil/Leucovorin (Folfiri) Plus Bevacizumab As First-Line Treatment In Patients With Metastatic Colorectal Cancer: A Randomized Phase Iii Trial Of The Hellenic Cooperative Oncology Group (Hecog).

3541 Background: The purpose of the trial was to compare two standard chemotherapy regimens combined with bevacizumab (Bev) in patients with metastatic colorectal cancer. Methods: Patients previously untreated for metastatic disease were randomized in: Arm A (irinotecan 240 mg/m2 day 1, capecitabine 1,000 mg/m2 days 1-14 and Bev 7.5 mg/kg day 1, every 3 weeks; XELIRI-Bev) and Arm B (irinotecan 180 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 400 mg/m2 bolus on day 1 followed by a fluorouracil 2,400 mg/m2 46 hours infusion, and Bev 5 mg/kg day 1, every 2 weeks; FOLFIRI-Bev). Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response and toxicity. Results: From January 2006 to January 2008, 285 eligible patients were enrolled (143 in arm A, 142 in arm B). Median age was 66 years (range 28-84), 171 patients (60%) were males and 186 (65%) had PS (ECOG) = 0. The liver was involved in 190 patients (67%), while 153 (54%) had only one organ involved. Fifty-five patients (38%, CR = 4%, PR = 34%) in arm A and 57 (40%, CR = 3%, PR = 37%) in arm B had responded (p = 0.81), whereas 28 patients (20%) in arm A and 40 (28%) in arm B had stable disease. After a median follow-up of 28.7 months (0.2-43.8), 86 vs 102 disease progressions, and 81 vs 75 deaths had occurred in arms A and B, respectively. Median PFS was 14.6 (95% CI = 12.4-16.7) and 15.8 (95% CI = 13.4-18.2) months (p = 0.48), while median OS was 20.0 (95% CI = 16.7-23.3) and 26.2 (95% CI = 22.0-30.4) months (p = 0.14), for arms A and B, respectively. Most frequent grade 3-4 toxicities (arm A vs. arm B) were neutropenia (12% vs. 22%, p = 0.048), leucopenia (6% vs. 4%), diarrhea (18% vs. 11%), metabolic disorders (8% vs. 18%, p = 0.028), and vomiting (7% vs. 0%, p = 0.014). Conclusions: This trial did not show significant differences in efficacy between XELIRI-Bev and FOLFIRI-Bev in patients with metastatic colorectal cancer treated in the first-line setting. However, the toxicity profile was different. Translational research on angiogenesis factors is ongoing. No significant financial relationships to disclose.