Shortened Adjuvant Treatment Duration Reduced Toxicity Without Impacting Efficacy in Colon Cancer

Findings from the phase 3 ACHIEVE trial indicated that 3 months of treatment with adjuvant oxaliplatin (Eloxatin) and fluoropyrimidine-based therapy vs 6 months in Asian patients with curatively resected stage III colon cancer highlighted a reduction in long-lasting peripheral sensory neuropathy without compromising efficacy.

The trial examined a modified regimen of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) as well as capecitabine (Xeloda) and oxaliplatin (CAPOX) in the adjuvant setting. The 2 treatment durations resulted in similar 5-year rates of overall survival (OS) across a population of 1291 patients, including 87.0% (95% CI, 84.2%-89.4%) in the 3-month group vs 86.4% (95% CI, 83.5%-88.9%) in the 6-month group (HR 0.91; 95% CI, 0.69-1.20; P = .51). There was no significant interaction between baseline characteristics and treatment duration according to an OS subgroup analysis. Additionally, any-grade peripheral sensory neuropathy (PSN) lasting longer than 5 years affected 8% of patients in the 3-month group vs 16% of those in the 6-month group (OR 0.424; 95% CI, 0.248-0.723; P = .0016); the toxicity was also more common in those receiving mFOLFOX6 (14%) vs CAPOX (11%; OR, 1.380; 95% CI, 0.780-2.443; P = .27).

“For OS, the final IDEA collaboration analysis failed to confirm the noninferiority of 3 vs 6 months of adjuvant chemotherapy for patients with stage III colon cancer, although the absolute difference in 5-year rates was only 0.4%,” the investigators wrote. “However, our analysis indicated that 5-year OS rates were comparable in the 3-month and 6-month treatment groups, with an HR of 0.91…. Three months of CAPOX therapy is therefore an appropriate treatment option in this setting, especially in patients with low-risk disease.”

This multicenter, open-label trial randomly assigned patients 1:1 to receive either 3 months (n = 650) or 6 months (n = 641) of adjuvant therapy, and were stratified according to quantity of involved lymph nodes, participating center, regimen, primary site, and age. The treating physicians selected between mFOLFOX6 and CAPOX for each patient before registration. Notably, switching regimens was not permitted. Most patients overall were under 70 years old with a minority of patients 70 years or older (65.5% vs 34.5%), received CAPOX as opposed to mFOLFOX6 (75.1% vs 24.9%), and had an ECOG performance status of 0 vs 1 (96.4% vs 3.6%). The trial examined male and female patients in nearly equal measure, respectively (50.3% vs 49.7%).

Efficacy outcomes were consistently comparable between the 2 cohorts at a median follow-up of 74.7 months. Across treatment arms, 148 patients in the 6-month group and 145 in the 3-month group experienced recurrence. Investigators also reported 5-year disease-free survival rates of 75.2% (95% CI, 71.7%-78.4%) in the 3-month group vs 74.2% (95% CI, 70.6%-77.5%) in the 6-month group (HR 0.95; 95% CI, 0.77-1.18; P = .64). Patients with high-risk disease experienced similar OS outcomes regardless of treatment duration; this was true for those treated with mFOLFOX6 (HR 0.91; 95% CI, 0.50-1.65; P = .75) and CAPOX (HR 0.99; 95% CI, 0.65-1.50; P = .95).

However, there were exceptions to this pattern. Findings from an analysis identified an association between worse outcomes with 3 months vs 6 months of mFOLFOX6 treatment in patients with low-risk disease (HR 1.26; 95% CI, 0.54-2.94; P = .60). However, patients with low-risk disease treated with 3 months of CAPOX vs 6 months had better outcomes (HR 0.70; 95% CI, 0.45-1.09; P = .11).

The 3-month treatment duration demonstrated an improved safety profile vs the 6-month duration. PSN of any grade occurred in 73% of patients in the 3-month group vs 82% in the 6-month group (OR 0.589; 95% CI, 0.451-0.768; P = .0001). Moreover, investigators recorded only a single event of grade 2 PSN in the 3-month group vs 5 patients of grade 2/3 PSN events in the 6-month group (OR 0.176; 95% CI, 0.020-1.517; P = .11).

Reference

Yoshino T, Oki E, Misumi T, et al. Final analysis of 3 versus 6 months of adjuvant oxaliplatin and fluoropyrimidine-based therapy in patients with stage III colon cancer: the randomized phase III ACHIEVE trial. J Clin Oncol. 2022;40(29):3419-3429. doi:10.1200/JCO.21.02628