Safety and efficacy of bevacizumab (Bev) when added to oxaliplatin/fluoropyrimidine (O/F) regimens as first-line treatment of metastatic colorectal cancer (mCRC): TREE 1 & 2 Studies

Abstract

3515 Background: Bevacizumab (Bev) added to IFL combination chemotherapy improves survival in mCRC. This randomized study assesses the safety & tolerability of each of three Oxaliplatin plus fluoropyrimidine regimens (bolus (b), infusional or oral fluoropyrimidine) alone in TREE1, and with Bev in TREE2. Methods: Eligibility: age ≥ 18; measurable untreated mCRC; PS ≤1. Primary endpoint: Grade 3/4 toxicities in the 1st 12 weeks (wk) of Rx; secondary endpoints: TTP, OS. Oxali-FU (in mg/m2) regimens consisted of: FOLFOX = O 85, leucovorin (LV) 350mg, 5FU bolus 400 & 2400 CIV x 46 hrs q 2 wk; bFOL = O 85 days (d) 1&15, LV 20 & bolus 5FU 500 d 1,8,15 q 4 wk; CapOx = O130 d 1, Capecitabine 1000 bid (850 for TREE2) for 14 d q 3 wk; Bev was added to each regimen (5 mg/kg q 2 wk or 7.5 mg/kg q 3 wk) in TREE2. Results: 147 pts were entered in TREE1 and 213 pts in TREE2. Selected gr 3/4 toxicity during 1st 12 wks of treatment is shown in table. Addition of B in TREE 2 caused increased gr 3/4 hypertension, impaired wound healing (5%) and bowel perforation (3%) in each arm. Confirmed ITT ORR (TREE1/2 respectively) = FOLFOX 39%/49%, bFOL 20%/34%, CapOx 29%/43% Conclusions: Grade 3–4 toxicity with first line Bev plus Oxaliplatin-based chemotherapy is acceptable and less than reported for IFL. All regimens of fluoropyrimidine administration are active but FOLFOX has best balance of response and toxicity. CapOX tolerance improved using reduced Cap 850 mg/m2 bid. Bev significantly improved RR (p=0.011, pooled logistic regression analysis) when added to Oxaliplatin-fluoropyrimidine chemotherapy. Additional efficacy data (TTP; OS) is not mature at time of abstract, but will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, sanofi-aventis Genentech, sanofi-aventis Genentech Genentech, Sanofi, sanofi-aventis Genentech, sanofi-aventis