Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): Final analysis of the TREE-Study

Abstract

3510 Background: The addition of bevacizumab (bev) to fluorouracil-based combination chemotherapy results in statistically significant improvement in survival among patients (pts) with mCRC. This randomized, multicenter trial was designed to assess the safety, tolerability and efficacy of each of three oxaliplatin (OX) plus bolus (b), infusional, or oral fluoropyrimidine (FP) regimens without (TREE1 cohort) or with (TREE2 cohort) bev for 1st line tx of mCRC. Methods: Eligibility included age ≥ 18 years, measurable, untreated mCRC, ECOG performance status ≤1. Primary endpoint: incidence of grade (gr) 3–4 toxicities (tox) on each arm during the 1st 12 weeks of therapy; secondary endpoints: ORR, TTP, OS. Regimens TREE-1: FOLFOX: OX 85mg/m2, leucovorin (LV) 350mg, 5-FU bolus 400mg/m2 and 2400mg/m2 CIV over 46 hours ; bFOL : OX 85mg/m2 days (d) 1&15, LV 20 mg/m2 and bolus 5-FU 500mg/m2 d 1,8,15 q 4 wks; CapeOx: OX 130 mg/m2 d 1, Capecitabine 1000–850 mg/m2 bid for 14 d. In TREE-2 bev 5 mg/kg q14 or 7.5 q 21 d was added. Results: 147 pts were treated in TREE1 and 213 treated in TREE2. Overall, incidence of any gr 3–4 toxicity (TREE1 vs. TREE2 respectively) = FOLFOX 75% vs. 66%, bFOL 42% vs. 59%, CapeOx 73% vs. 54%. Addition of bev in TREE2 caused more gr 3–4 hypertension, impaired wound healing, and bowel perforation in each arm. Confirmed ITT ORR (TREE1 vs TREE2 respectively) = FOLFOX 41% vs.52%, bFOL 20% vs.39%, CapeOx 27% vs. 46%. Median TTP (months) + 95% CI (TREE1 vs TREE2 respectively) = FOLFOX 8.7 (6.5, 9.8) vs. 9.9 (7.9, 11.7), bFOL 6.9 (4.2, 8.0) vs. 8.3 (6.6, 9.9), CapeOx 5.9 (5.1, 7.4) vs.10.3 (8.6, 12.5). Probability of survival at 18 months (TREE1 vs. TREE2 respectively) = FOLFOX 53% vs. 63%, bFOL 50% vs. 63%, CapeOx 49% vs. 68%. As of January 9, 2006, 56 TREE1 pts (38%) and 122 TREE2 pts (57%) are alive. Conclusions: These data demonstrate these three Ox/FP regimens to be tolerable and effective. Addition of bev to Ox/FP regimens improves response rate and TTP with acceptable tolerability, and no unexpected toxicity. [Table: see text]