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

Research output: Contribution to journalArticle

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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

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oxaliplatin
irinotecan
Colonic Neoplasms
Disease-Free Survival
Cytotoxins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: European Journal of Cancer, Vol. 47, No. 7, 05.2011, p. 990-996.

Research output: Contribution to journalArticle

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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.",
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AU - Sargent, D.

AU - Shi, Qian D

AU - Yothers, G.

AU - Van Cutsem, E.

AU - Cassidy, J.

AU - Saltz, L.

AU - Wolmark, N.

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AU - Grothey, Axel F

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