Adjuvant FOLFOX or CAPOX for 3 or 6 Months in Stage II or III Colon Cancer
As reported in the Journal of Clinical Oncology by Sobrero et al, the Italian phase III TOSCA trial did not demonstrate noninferiority of 3 vs 6 months of adjuvant CAPOX (capecitabine plus oxaliplatin) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) in relapse-free survival in stage II or stage III colon cancer.
Study Details
Data from TOSCA were analyzed before the target number of relapse-free survival events were achieved, due to the decision to include findings with those of five other trials in the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) initiative.
In the open-label trial, 3,759 patients from 130 sites were randomized between June 2007 and March 2013 to receive 3 months of standard doses of FOLFOX4 or CAPOX (n = 1,175) or 6 months of FOLFOX4 or CAPOX (n = 1,839), with 64% of patients receiving FOLFOX and 36% receiving CAPOX in either group. Randomization was stratified by stage II and stage III disease, with two-thirds of patients having stage III disease.
Relapse-Free Survival
Median follow up was 62 months. The hazard ratio for relapse-free survival for 3 vs 6 months of treatment was 1.14 (95% confidence interval [CI] = 0.99–1.32; P = .514 for noninferiority), with the confidence interval crossing the noninferiority limit of 1.20. However, the absolute difference in 3-year relapse-free survival was small (1.9%). Hazard ratios for 3 vs 6 months of treatment were 1.07 (95% CI = 0.91–1.26) for stage III disease, 0.98 (95% CI = 0.77–1.26) among patients receiving CAPOX, 1.41 (95% CI = 1.05–1.89) in stage II disease, and 1.23 (95% CI = 1.03–1.46) among patients receiving FOLFOX.
The investigators concluded, “The Three or Six Colon Adjuvant [TOSCA] trial failed to formally show noninferiority of 3 vs 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counterintuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy…. [B]ecause the results of TOSCA on substages are counterintuitive, they should be interpreted with caution within the context of the combined analyses of IDEA.”
The study was supported by a grant from the Agenzia Italiana del Farmaco.
Alberto Sobrero, MD, of Ospedale Policlinico San Martino, Genova, is the corresponding author for the Journal of Clinical Oncology article.
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