Oxaliplatin-Based Adjuvant Chemotherapy Duration (3 vs. 6 Months) for High-Risk Stage II Colon Cancer: The Randomized Phase 3 ACHIEVE-2 Trial

Abstract Background Oxaliplatin-based adjuvantchemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk colon cancer. This open-label, multicenter, randomized phase 3 trial was as a prospective pooled analysis conducted to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy in stage II disease. Patients and methods From February 12, 2014 to January 31, 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary endpoint was disease-free survival (DFS). The secondary endpoints were treatment compliance and safety. Results Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm (hazard ratio [HR], 1.12; 95% CI, 0.67–1.87). With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65–1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P Conclusions Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option.