Bevacizumab (B) + bi-weekly capecitabine (C) and oxaliplatin (O) (XELOX2) or FOLFOX4 in first-line treatment of metastatic colorectal cancer (mCRC): Final results of a multicenter randomized phase II trial of the Gruppo Oncologico dell’Italia Meridionale (GOIM protocol 2802).

3542 Background: B plus bi-weekly FOLFOX4 or three-weekly XELOX represents a standard 1-line therapy for mCRC pts. In our previous phase II study (Fedele P et al, ASCO 2009) we demonstrated a similar efficacy of a bi-weekly schedule of C combined with O (XELOX2). In this randomized phase II trial, pts with mCRC, previously untreated, ECOG PS 0-1, age 18-75, were randomized to receive, in a 2:1 ratio, XELOX2 + B (experimental arm) vs. FOLFOX4 + B (calibration arm). Primary endpoint was ORR; secondary endpoints were PFS, OS and toxicity. Methods: B (5 mg/kg on d1 of a 2-week cycle) was administered before O, with FOLFOX4 (Arm A) or XELOX-2 (Arm B; O 100 mg/m2 on d1 followed by oral C 1,000 mg/m2 twice daily on d1 through 7 of a 14-day cycle). After a maximum of 12 cycles (induction phase), pts in CR,PR and SD were randomized to maintenance with B alone or B+Fluoropyrimidine (C or FU). Sample size of experimental arm was calculated according to Simon's two-stage design, with a type I error rate 0.05 and 0.90 power. With null hypothesis ORR 32% and alternative hypothesis ORR 48%, 46 pts had to be accrued in the first stage, for a final number of 80 pts. Study design was formally non comparative, but exploratory comparison between arms was performed. Results: One-hundred thirty-two pts were randomized (45 arm A; 87 arm B). The main characteristics of the entered pts were well balanced. ORR (Arm A vs B) was 55.6% vs 48.3% (p = 0.43). With a median follow-up of 47.2 months, PFS was 10.0 vs 9.9 months (HR 0.96, 95%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). Main G3-4 toxicity rate (A vs B) were as follows: thrombocytopenia 2/2, anemia 4/3, neutropenia 15/3, nausea 9/5. vomiting 2/3, diarrhea 7/7, neurotoxicity 2/2 and hypertension 2/1. Conclusions: GOIM study 2802 showed that the XELOX2+B regimen is active as FOLFOX4+B in pts with mCRC. Given the extreme tolerability and convenience of administration of therapy, XELOX2 + B appears to be indicated even in frail or elderly patients. Clinical trial information: 2010-022091-31.