Adjuvant Chemotherapy Duration in Stage III Colon Cancer


Key Points

  • 3 months of either FOLFOX or CAPOX was not noninferior to 6 months in disease-free survival.
  • 3 months of CAPOX was noninferior to 6 months.

In a preplanned pooled analysis of phase III trials reported in The New England Journal of Medicine, Grothey et al did not establish noninferiority of 3 vs 6 months of adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) in disease-free survival in stage III colon cancer but found noninferiority of 3 vs 6 months of CAPOX in separate analysis.  

Study Details

The preplanned pooled analysis, as part of the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration, included 6 phase III trials conducted concurrently between June 2007 and December 2015 to evaluate the noninferiority of adjuvant FOLFOX or CAPOX given for 3 vs 6 months. The primary endpoint was the rate of disease-free survival at 3 years. Noninferiority of 3 vs 6 months of therapy was established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) did not exceed 1.12. In total, the analysis included 12,834 patients, including 3,870 and 3,893 receiving FOLFOX for 3 and 6 months and 2,554 and 2,517 receiving CAPOX for 3 and 6 months.

Disease-Free Survival

After 3,263 events of disease recurrence or death had been reported in 12,834 patients, at median follow-up of 41.8 months, the noninferiority of 3 months of FOLFOX or CAPOX treatment vs 6 months was not confirmed (HR = 1.07, 95% CI = 1.00–1.15, P = .11 for noninferiority; P = .045 for superiority of 6 months). The 3-year rate of disease-free survival was 74.6% in the 3-month group vs 75.5% in the 6-month group. Three months of treatment was noninferior to 6 months for CAPOX (HR = 0.95, 95% CI = 0.85–1.06) but not for FOLFOX (HR = 1.16, 95% CI = 1.06–1.26).

In exploratory analysis, 3 months of therapy with either regimen was noninferior to 6 months among patients with T1, T2, or T3 and N1 cancers, with 3-year disease-free survival of 83.1% vs 83.3% for 3 vs 6 months (HR = 1.01, 95% CI = 0.90–1.12). Among patients with T4 or N2 disease or both, 6 months of therapy was superior to 3 months, with 3-year disease-free survival of 64.4% vs 62.7% (HR = 1.12, 95% CI = 1.03–1.23; P = .01 for superiority).

The investigators concluded, “Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup.”

The study was funded by the National Cancer Institute and others.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.