A new look at the International Duration Evaluation of Adjuvant therapy (IDEA) classification—Defining novel predictive and prognostic markers in stage III colon cancer

Background: The International Duration Evaluation of Adjuvant therapy (IDEA) pooled analysis compared 3 to 6 months of adjuvant chemotherapy for stage III colon cancer. The overarching goal was to reduce chemotherapy-related toxicity, mainly oxaliplatin-induced neuropathy. Patients were classified into low-risk and high-risk groups, suggesting that low-risk patients may be offered only 3 months of treatment. We aimed to evaluate the benefit of monotherapy versus doublet chemotherapy in low and high IDEA risk groups. Methods: Using the National Cancer Database (2004–2014), we identified 56,728 low-risk and 47,557 high-risk individuals with stage III colon cancer, according to the IDEA classification. We used multivariate Cox regression to evaluate the magnitude of survival differences between IDEA risk groups, according to treatment intensity (doublet versus monotherapy). In a secondary analysis, we examined the prognostic and predictive value of subgroups of age, tumour sidedness and lymph node ratio (LNR). Results: Low and high IDEA risk groups derived similar benefit from doublet adjuvant chemotherapy as compared with monotherapy, with hazard ratios (HRs) of 0.83 (95% confidence interval [CI] 0.79–0.86) and 0.80 (95% CI 0.78–0.83), respectively. The only subpopulations that did not benefit from doublet chemotherapy were low-risk patients older than 72 years (HR = 0.95, 95% CI 0.90–1.01) and high-risk patients older than 85 years (HR = 0.90, 95% CI 0.77–1.05). LNR and tumour sidedness were shown as additional prognostic, but not predictive, factors within the IDEA risk groups. Conclusions: IDEA risk classification per se does not predict for treatment benefit from doublet chemotherapy in stage III colon cancer. However, omission of oxaliplatin can be considered in IDEA low-risk patients older than 72 years.