Adjuvant Chemotherapy Duration in Stage III Colon Cancer
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.
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