Randomised phase III trial of capecitabine + oxaliplatin vs. bolus 5-FU/LV for stage III colon cancer (NO16968): impact of age on disease-free survival (DFS) or overall survival (OS)

Abstract:	4224
Congress:	ESMO 2010
Type:	Abstract
Topic:	Colorectal cancer
Authors:	D. Haller1, J. Cassidy2, J. Tabernero3, J. Maroun4, F. De Braud5, T. Price6, E. van Cutsem7, M. Hill8, F. Gilberg9, H.-J. Schmoll10; 1Philadelphia/United States of America, 2Glasgow/United Kingdom, 3Barcelona/Spain, 4Ottawa/Canada, 5Milano/Italy, 6Adelaide/Australia, 7Leuven/Belgium, 8Maidstone/United Kingdom, 9Basel/Switzerland, 10Halle/Germany

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  Background: Adjuvant capecitabine is at least equivalent to bolus i.v. 5-FU/LV. NO16968 compared XELOX with bolus i.v. 5-FU/LV for stage III colon cancer. In a planned safety analysis, XELOX had an acceptable safety profile [Schmoll et al. 2007]. In a recent analysis of the ACCENT database, investigators concluded that the improved efficacy associated with newer adjuvant regimens vs. 5-FU/LV may not be preserved in patients (pts) ≥70y [McCleary et al. 2009].

  Methods: Pts were randomized to either XELOX (capecitabine 1000mg/m² bid d1–14 + oxaliplatin 130mg/m² i.v. d1, q3w x8) or bolus i.v. 5-FU/LV: Mayo Clinic (LV 20mg/m² + 5-FU 425mg/m² d1–5, q4w x6) or Roswell Park (LV 500mg/m² + 5-FU 500mg/m² d1, w1–6 in 8w cycles x4). Treatment effects of XELOX vs. 5-FU/LV were assessed by age (≥65y, planned; ≥70y, unplanned).

  Results: Of the 1886 pts randomized, 1864 were evaluable in the previously reported safety analysis. After median follow-up of 57 months, 1886 pts (ITT) were evaluated for DFS (primary endpoint), which was significantly superior for XELOX (HR=0.80; 95% CI, 0.69–0.93, p=0.0045). Analysis of 3-y DFS and 5-y OS in pts <70y and ≥70y showed a similar advantage of XELOX over 5-FU/LV.

  
  

  	3-y DFS	4-y DFS	5-y DFS
  Total population
  XELOX	70.9%	68.4%	66.1%
  5-FU/LV	66.5%	62.3%	59.8%
  	DFS by age group	OS by age group
  Overall	HR 0.80 (95% CI, 0.69–0.93)	HR 0.87 (95% CI, 0.72–1.05)
  <70y	HR 0.79 (95% CI, 0.66–0.94)	HR 0.86 (95% CI, 0.69–1.08)
  ≥70y	HR 0.87 (95% CI, 0.63–1.18)	HR 0.94 (95% CI, 0.66–1.34)

  Conclusions: XELOX is superior to bolus 5-FU/LV for DFS as adjuvant treatment for stage III colon cancer; these findings confirm the benefits shown with oxaliplatin plus 5-FU combinations in stage III pts. Efficacy benefits are maintained for DFS and OS in pts ≥70y, in contrast to results from ACCENT and MOSAIC, in which no significant benefit was shown with the addition of oxaliplatin to 5-FU/LV in this age group. Reasons for this apparent difference are unknown. Current OS data indicate a trend towards superior survival with XELOX. XELOX is an effective adjuvant therapy and should be considered for all eligible patients.