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. 2020 Apr;31(4):480-486.
doi: 10.1016/j.annonc.2019.12.007. Epub 2020 Jan 16.

Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database

M E Salem  1 , J Yin  2 , R M Goldberg  3 , L D Pederson  2 , N Wolmark  4 , S R Alberts  5 , J Taieb  6 , J L Marshall  7 , S Lonardi  8 , T Yoshino  9 , R S Kerr  10 , G Yothers  11 , A Grothey  12 , T Andre  13 , A De Gramont  14 , Q Shi  15
Affiliations

Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database

M E Salem et al. Ann Oncol. 2020 Apr.

Abstract

Background: Since 2004, adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX or FLOX) have been the standard of care for patients with resected colon cancer. Herein we examine the change of outcomes over a 10-year period in patients with stage III colon cancer who received this regimen.

Patients and methods: Individual patient data from the ACCENT database was used to compare the outcomes in older (1998-2003) and newer (2004-2009) treatment eras for patients with stage III colon cancer who received adjuvant FOLFOX or FLOX. The outcomes were compared between the two groups by the multivariate Cox proportional-hazards model adjusting for age, sex, performance score, T stage, N stage, tumor sidedness, and histological grade.

Results: A total of 6501 patients with stage III colon cancer who received adjuvant FOLFOX or FLOX in six randomized trials were included in the analysis. Patients enrolled in the new era group experienced statistically significant improvement in time to recurrence [3-year rate, 76.1% versus 73.0%; adjusted hazard ratio (HRadj) = 0.83 (95% CI, 0.74-0.92), P = 0.0008], disease-free survival (DFS) [3-year rate, 74.7% versus 72.3%; HRadj = 0.88 (0.79-0.98), P = 0.024], survival after recurrence (SAR) [median time, 27.0 versus 17.7 months; HRadj = 0.65 (0.57-0.74), P < 0.0001], and overall survival (OS) [5-year rate, 80.9% versus 75.7%; HRadj = 0.78 (0.69-0.88), P < 0.0001]. The improved outcomes remained in patients diagnosed at 45 years of age or older, low-risk patients (T1-3 and N1), left colon, mismatch repair proficient (pMMR), BRAF, and KRAS wild-type tumors.

Conclusion: Improved outcomes were observed in patients with stage III colon cancer enrolled in clinical trials who received adjuvant FOLFOX/FLOX therapy in 2004 or later compared with patients in the older era. Prolonged SAR calls for revalidation of 3-year DFS as the surrogate endpoint of OS in adjuvant clinical trials and reevaluation of optimal follow-up of OS to confirm the trial findings based on the DFS endpoints.

Clinical trials numbers: NCT00079274; NCT00096278; NCT00004931; NCT00275210; NCT00265811; NCT00112918.

Keywords: FOLFOX; adjuvant; colon cancer; disease-free survival; overall survival; stage III.

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Conflict of interest statement

Disclosure The authors have declared no conflicts of interest.

Figures

Figure 1.
Figure 1.
Comparing Clinical Outcomes between Newer and Old Era Trials. Abbreviations: KM=Kaplan-Meier; DFS=Disease-Free Survival; TTR=Time-to-Recurrence; SAR=Survival after Recurrence; OS=Overall Survival.
Figure 2.
Figure 2.
Comparing outcomes between time eras (newer versus old) by subpopulations. Abbreviations: DFS=Disease-Free Survival; TTR=Time-to-Recurrence; SAR=Survival after Recurrence; OS=Overall Survival; HR=Hazard Ratio; MT=Mutant Type; WT=Wild Type.
Figure 2.
Figure 2.
Comparing outcomes between time eras (newer versus old) by subpopulations. Abbreviations: DFS=Disease-Free Survival; TTR=Time-to-Recurrence; SAR=Survival after Recurrence; OS=Overall Survival; HR=Hazard Ratio; MT=Mutant Type; WT=Wild Type.
Figure 2.
Figure 2.
Comparing outcomes between time eras (newer versus old) by subpopulations. Abbreviations: DFS=Disease-Free Survival; TTR=Time-to-Recurrence; SAR=Survival after Recurrence; OS=Overall Survival; HR=Hazard Ratio; MT=Mutant Type; WT=Wild Type.
Figure 2.
Figure 2.
Comparing outcomes between time eras (newer versus old) by subpopulations. Abbreviations: DFS=Disease-Free Survival; TTR=Time-to-Recurrence; SAR=Survival after Recurrence; OS=Overall Survival; HR=Hazard Ratio; MT=Mutant Type; WT=Wild Type.
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