Final Analysis of 3 vs 6 Months of Adjuvant FOLFOX or CAPOX for Stage III Colon Cancer

Fluoropyrimidine-based adjuvant therapy for resected stage III colon cancer became standard of care in 1990 when the use of postoperative 5-fluorouracil (5-FU) plus levamisole was shown to be superior to surgery alone. At that time, the duration of adjuvant therapy was 12 months. In 2005, the final publication of the INT-0089 trial showed that 6 months of bolus 5-FU/leucovorin (LV) provided outcomes similar to those of 12 months of 5-FU/levamisole. By that time, however, the standard of care for adjuvant therapy had already moved toward an oxaliplatin-based regimen when the MOSAIC trial demonstrated superior disease-free survival (DFS) for FOLFOX over that for infusion or bolus 5-FU/LV. Unfortunately, a 6-month duration of oxaliplatin-based therapy comes at a price of significant and potentially debilitating sensory neurotoxicity, which is why, more recently, the IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration prospectively tested the question of whether 3 months of oxaliplatin-based adjuvant therapy was noninferior to 6 months. Six trials were conducted by this collaboration, with the eventual inclusion of 12,835 patients. Unexpectedly, the final results showed that, when using capecitabine/oxaliplatin (CAPOX) as adjuvant therapy, a 3-month duration was noninferior to a longer duration of therapy in most clinical scenarios, which was not the case for FOLFOX. Thus, for most patients with stage III colon cancer, 3 months of CAPOX became the practice standard of care. The IDEA collaboration precluded individual data from the six trials to be published before the joint analysis. We are now seeing the intriguing results of the Japanese ACHIEVE study, which contributed 1291 patients to the IDEA collaboration. In the final DFS and overall survival analysis presented, a 3-month duration of adjuvant therapy resulted in outcomes comparable with those of a longer treatment duration for all parameters. Of note in this context is that, in Japan, 75% of patients received CAPOX, and only 25% received FOLFOX. No difference in outcome for a shorter duration of therapy was seen for conventionally staged high- versus low-risk stage III cancers. The data from the ACHIEVE trial also showcase the excellent overall outcomes of Japanese patients with resected colon cancers, which in international comparison, are at the top end of published results. In conclusion, the data from the ACHIEVE trial support the use of 3 months of CAPOX as standard adjuvant therapy for the vast majority of patients with resected stage III colon cancer.