Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: Data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803

D. Sargent, Q. Shi, G. Yothers, E. Van Cutsem, J. Cassidy, L. Saltz, N. Wolmark, B. Bot, A. Grothey, M. Buyse, A. De Gramont

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Background: The ACCENT group previously established disease-free survival (DFS) with 2 or 3 years median follow-up to predict 5 year overall survival (5 year OS) in stage II and III colon cancer. ACCENT further proposed (1) a stronger association between DFS and OS in stage III than II, and (2) 6 or 7 years necessary to demonstrate DFS/OS surrogacy in recent trials. The relationship between end-points in trials with oral fluoropyrimidines, oxaliplatin and irinotecan is unknown. Methods: Associations between the treatment effect hazard ratios (HRs) on 2 and 3 years DFS, and 5 and 6 years OS were examined in 6 phase III trials not included in prior analyses from 1997 to 2002. Individual data for 12,676 patients were analysed; two trials each tested oxaliplatin, irinotecan and oral treatment versus 5-FU/LV. Findings: Overall association between 2/3 year DFS and 5/6 year OS HRs was modest to poor (simple R2 measures: 0.58-0.76, model-based R2: 0.17-0.49). In stage III patients, the association increased (model-based R2 ≥ 0.79). Observed treatment effects on 2 year DFS accurately 5/6 year OS effects overall and in stage III patients. Interpretation: In recent trials of cytotoxic chemotherapy, 2 or 3 years DFS HRs are highly predictive of 5 and 6 years OS HRs in stage III but not stage II patients. In all patients the DFS/OS association is stronger for 6 year OS, thus at least 6 year follow-up is recommended to assess OS benefit. These data support DFS as the primary end-point for stage III colon cancer trials testing cytotoxic agents.

Original languageEnglish (US)
Pages (from-to)990-996
Number of pages7
JournalEuropean Journal of Cancer
Volume47
Issue number7
DOIs
StatePublished - May 2011

Keywords

  • Adjuvant therapy
  • Clinical trial end-points
  • Colon cancer
  • Disease-free survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: Data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803'. Together they form a unique fingerprint.

  • Cite this