FOLFIRI plus 5 mg/kg of bevacizumab versus 10 mg/kg as second-line therapy in patients with metastatic colorectal cancer who have failed first-line bevacizumab plus oxaliplatin-based therapy: A randomized phase III study (EAGLE Study).

Abstract

TPS3642 Background: There has been much controversy about continuation of bevacizumab (BV) with a second-line regimen after progression on a BV-containing first-line regimen. Recently, it was announced that a phase III study (AIO 0504 / ML 18147) met its primary endpoint of overall survival. It means BV-based regimen (5 mg/kg) extends survival when continued beyond initial treatment in patients with metastatic colorectal cancer(mCRC). The verified data from a randomized phase III study (E3200) indicates that BV at 10 mg/kg in the second-line setting followed by BV-naive treatment extends survival. The dose of BV 5 mg/kg could be lower than the recommended dose in the second-line CRC treatment. Thus we planned this second line phase III study (EAGLE study) to evaluate the appropriate dose of BV (5 or 10 mg/kg) with FOLFIRI in patients with mCRC who have failed BV plus oxaliplatin-based first line regimen. Methods: EAGLE is a multicenter randomized phase III study of FOLFIRI plus BV 5 mg/kg versus 10 mg/kg in mCRC who have failed BV plus oxaliplatin-based first line regimen (UMIN000002557).The primary endpoint is PFS. The secondary endpoints are the toxicity, response rate, time to treatment failure, OS. Eligible patients were older than 20 years of age, had histologically proved CRC, ECOG performance status 0 or 1, adequate organ function, progression or difficult to continue after BV plus oxaliplatin-based first line regimen, more than four times administration of BV and oxaliplatin in the first-line. Patients were randomized 1:1 to FOLFIRI with BV 5mg/kg or 10 mg/kg.The planned sample size was 370 patients to detect 30% risk reduction (median PFS assumed to be 5.0 months in arm A, 7.0 months in arm B) with 90% power assuming a two-sided significance level of 0.05, an accrual time of 2.5 years and a follow-up time of 1 year. Between September 2009 to January 2012, 387 patients were enrolled at 100 sites in Japan. This phase III study will answer the question of the appropriate dose of BV after progression on a BV-containing first-line regimen.