Bevacizumab in combination with either FOLFOX-4 or XELOX-2 in first-line treatment of patients with metastatic colorectal cancer: A multicenter randomized phase II trial of the Gruppo Oncologico dell’Italia Meridionale (GOIM 2802)

Abstract Introduction Biweekly schedule of capecitabine plus oxaliplatin (XELOX-2) showed interesting results in first-line therapy of metastatic colorectal cancer (mCRC) patients. Bevacizumab plus oxaliplatin, folinic acid and infusional 5-fluorouracil (FOLFOX-4) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of mCRC patients. Materials and Methods mCRC patients were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. Primary endpoint was objective response rate (ORR), secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Study design was formally non-comparative, but exploratory comparison was performed. Results 45 patients were randomized in arm A and 87 in arm B with an ORR of 55.6% vs. 48.3% (p = 0.43), respectively. After a median follow-up of 47.2 months, PFS was 10.0 vs. 9.9 months (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.65-1.41; p = 0.84) and OS was 29.8 vs. 25.0 months (HR 1.21, 95% CI 0.77-1.92; p = 0.41), respectively. The main grade 3-4 toxicities (% A/B) were: neutropenia 15/3, nausea 9/5. Conclusion This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has comparable ORR as FOLFOX-4 plus bevacizumab in patients with mCRC.