Long-term effect of peripheral sensory neuropathy (PSN) of 3 or 6 months oxaliplatin-based adjuvant chemotherapy for high-risk stage II colon cancer: ACHIEVE-2 as part of the …

The ACHIEVE-2 trial, a part of the IDEA collaboration, was a multicenter study randomizing patients with high-risk stage II resected colon cancer to either 3 or 6 months of mFOLFOX6/CAPOX. Previous our report in the ACHIEVE trial for stage III colon cancer patients (pts) showed that the incidence of long-lasting peripheral sensory neuropathy (PSN) was significantly lower for 3 months (3m) of therapy than for 6 months (6m) of therapy. More importantly, the incidence of long-lasting PSN was significantly lower for CAPOX than for FOLFOX. The present study aimed to evaluate the incidence of long-lasting PSN in the 3m arm as compared to the 6m arm in the ACHIEVE-2 trial. ACHIEVE-2 enrolled 514 patients. The incidence of PSN was evaluated every 3m up to three years. The grade of PSN was assessed using CTCAE ver 4.0. During the study treatment, PSN of grade 2/3 was observed more frequently in the 6m arm (36%/7%) than in the 3m arm (17%/1%). At two years from randomization, PSN of grade 1/2/3 lasted in 34%/2%/0% of pts in the 6m arm, whereas 20%/2%/0% of pts in the 3m arm. At three years, PSN of grade 1/2/3 lasted in 27%/2%/0% of pts in the 6m arm whereas 19%/1%/0% of patients in the 3m arm. Thus, PSN ≥ grade 1 was significantly less frequent in the 3m arm than in the 6m arm at two years (22% vs 36%, P=0.0049) and tended to be less frequent at three years (20% vs 29%, P=0.1630). Moreover, PSN ≥ grade 1 lasting for 3 years tended to be lower for CAPOX than for mFOLFOX6 in both the 3m (19% vs 25%, P=0.7375) and 6m arms (26% vs 47%, P=0.1252). The present study for high-risk stage II colon cancer showed that the incidence of long-lasting PSN was significantly lower for 3 months of therapy than for 6 months of therapy. Further, we confirmed a similar trend that the incidence was lower for CAPOX than for mFOLFOX6, although the result was not statistically significant due, possibly, to a lack of power. The role of regimen on long-lasting PSN is still a topic of ongoing debate and our result may warrant a further analysis using the whole data of the IDEA Collaboration.