XELOX compared to FOLFOX4: Survival and response results from XELOX-1/ NO16966, a randomized phase III trial of first-line treatment for patients with metastatic colorectal cancer (MCRC)

Abstract

4030 Background: In a phase II study in untreated MCRC patients, XELOX (capecitabine + oxaliplatin) appeared to have similar efficacy compared with previously published FOLFOX4 data [1]. We therefore started a phase III 2-arm open-label non-inferiority study comparing XELOX with FOLFOX4. In 2003 the addition of bevacizumab (Bev) to irinotecan/5-FU/LV was shown to improve progression-free survival (PFS) and overall survival [2]. We then amended our trial to a 2x2 partially blinded study to assess the addition of Bev. Methods: Original 2-arm study: XELOX (oxaliplatin 130 mg/m2 iv, capecitabine 1,000 mg/m2 bid oral d1- 14, q3w) vs. FOLFOX4 (oxaliplatin, 5-FU, leucovorin as described previously) [3]. In August 2003, amended to 2x2 partially blinded study: by adding Bev 7.5 mg/kg iv q3w or placebo (Pla) to XELOX and Bev 5 mg/kg iv q2w or Pla to FOLFOX4. Results: The original 2-arm study recruited 634 pts; after transition to 2x2, an additional 1400 patients were recruited. We previously reported non-inferiority in terms of PFS of XELOX vs. FOLFOX4 for the whole study population [4]. With 404 events, the overall survival data from the original 2-arm study are mature and show a HR for XELOX vs. FOLFOX4 of 0.93 (97.5% CI, 0.74–1.16). The response rates by investigator and independent review for the whole study population are shown in the table . Conclusions: XELOX is non-inferior to FOLFOX4. Overall survival data for the whole 2034 patient study population will be presented at the meeting. *no response assessment. 1. Cassidy J et al. J Clin Oncol 2004;22:2084–91. 2. Hurwitz H et al. N Eng J Med 2004;350:2335–42 3. De Gramont A et al. J Clin Oncol 2000;18:2938–47. 4. Cassidy J et al. Ann Oncol 2006;17(Suppl. 9):LBA3. [Table: see text] [Table: see text]