A phase II, double-blind, randomized multicenter study of cediranib with FOLFOX versus bevacizumab with FOLFOX in patients with previously treated metastatic colorectal cancer (mCRC): Final PFS results

Abstract

4028 Background: Cediranib (AZD2171) is an oral, highly potent and selective inhibitor of VEGF signaling, with activity against VEGFR-1, -2, and -3. Recent trials have shown that the combination of bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A (VEGF-A) with 5-fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (OX; FOLFOX) provides clinical benefit in patients with mCRC, in previously untreated (Saltz et al. Proc Am Soc Clin Oncol 2007; abst 4028) and previously treated (Giantonio et al. J Clin Oncol 2007;25:1,539) patients. This head-to-head study compares cediranib plus FOLFOX to bevacizumab plus FOLFOX in patients with mCRC who have failed initial therapy. Methods: Male and female patients (≥18 years) with adenocarcinoma of the colon or rectum, who had received one prior therapy for metastatic disease were randomized to one of the following treatment groups: cediranib 20 mg/day; cediranib 30 mg/day or bevacizumab 10 mg/kg every 2 weeks. All patients received mFOLFOX6 every 2 weeks (OX 85 mg/m2 and LV 400 mg/m2; followed by 5-FU 400 mg/m2 bolus and then 2,400 mg/m2). Patients were excluded if they had received prior OX in the previous 12 months, any prior VEGF-inhibitor therapy or had a history of uncontrolled hypertension or unstable brain metastases. The primary objective is to compare progression-free survival (PFS) of the three treatment groups. Secondary endpoints include overall response rate, overall survival, safety and quality of life. PFS will be analyzed when 120 progression events have been observed using a log-rank test, stratified by performance status (0 or 1/2), baseline albumin (<4 and ≥4 g/dL) and baseline alkaline phosphatase (≤160 and >160 u/L). Results: Between January 2006 and July 2007, 215 patients were randomized from 42 centers in 10 countries in Europe and Canada. Results will be available for presentation at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca AstraZeneca, Merck, Roche