Seven-year efficacy and safety in a randomized phase III trial investigating duration of adjuvant oxaliplatin-based therapy (3 vs. 6 months) for patients with high-risk stage II colon cancer: ACHIEVE-2 trial.

169 Background: ACHIEVE-2 was conducted as one of four phase III trials for patients with high-risk stage II colon cancer (CC) investigating the duration of adjuvant (adj) oxaliplatin-based therapy in a prospective pooled analysis, IDEA collaboration. The results of the 7-year follow-up are presented here. Methods: From Feb 2014 to Jan 2017, 525 Asian patients with high-risk stage II CC (T4, inadequate nodal harvest, poorly differentiated, obstruction, perforation, or vascular invasion) were randomly assigned to 3- or 6-month mFOLFOX6/CAPOX treatment after curative surgery. The cutoff date for the data was Jan 2024. Results: Of the 525 randomized patients, 11 were not treated. Among the 514 participants (255 in the 3-month arm; 259 in the 6-montharm), 432 (84%) received CAPOX and 184 (36%) presented with T4 as a high-risk factor for recurrence. The baseline characteristics of the patients in each arm were well balanced between the treatment arms and two therapy regimens. The 7-year disease-free survival (DFS) rates were 83.4% and 81.8% in the 3- and 6-month arms, respectively (hazard ratio [HR]= 1.00 [95% CI, 0.66-1.53]). The 7-year overall survival (OS) rates were 88.4% and 88.8% in the 3- and 6-month arms, respectively (HR= 1.16 [95% CI, 0.70-1.93]). With CAPOX, the HR for DFS and OS of the 3-month arm compared with the 6-month arm were 0.97 (95% CI, 0.61-1.52) and 1.09 (95% CI, 0.64-1.89), respectively. Multivariate analysis of the six high-risk factors for recurrence showed that T4 and inadequate nodal harvest were independent risk factors for both DFS and OS. The rates of any grade of peripheral sensory neuropathy (PSN) lasting up to 96 months in the 3- vs. 6-month arms were 7.9% vs. 25.0% ( P= 0.0189 ). With CAPOX, the incidence of PSN lasting up to 96 months in the 3- vs. 6-month arms were 9.4% vs. 27.5%. Conclusions: The incidence of long-lasting PSN was significantly lower at 3 months than at 6 months of therapy. Three months of CAPOX therapy may be appropriate for high-risk stage II CC, as shorter treatment did not worsen the outcome, even after a long follow-up. Clinical trial information: UMIN000013036 .