Shortened Adjuvant CAPOX Treatment Does Not Compromise Safety, Efficacy in Stage III Colon Cancer

Article

The phase 3 ACHIEVE trial analyzed Asian patients with stage III colon cancer to determine how a 3-month treatment duration with capecitabine and oxaliplatin compared with 6 months.

Treating Asian patients with stage III colon cancer with capecitabine and oxaliplatin (CAPOX) for 3 months vs 6 months did not negatively impact efficacy and even reduced long-lasting peripheral sensory neuropathy (PSN), according to findings from the phase 3 ACHIEVE trial published in The Journal of Clinical Oncology.

The 5-year overall survival (OS) rates were 87.0% (95% CI, 84.2%-89.4%) for the 3-month regimen and 86.4% (95% CI, 83.5%-88.9%; HR, 0.91; 95% CI, 0.69-1.20; P = .51) in the 6-month regimen. Patients who received modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) had 5-year OS rates of 83.2% (95% CI, 76.5%-88.2%) vs 84.6% (95% CI, 77.9%-89.4%) in the 3-month and 6-month treatment groups, respectively (HR, 0.99; 95% CI, 0.61 to 1.60; P = .95).Those who received CAPOX had 5-year OS rates of 88.3% (95% CI, 85.1%-90.9%) in the 3-month group and 87.0% (95% CI, 83.6%-89.7%) in the 6-month group (HR, 0.87; 95% CI, 0.62-1.22; P = .42).

A total of 1313 patients were enrolled to receive either 6 months (n = 656) or 3 months (n = 657) of oxaliplatin and fluoropyrimidine–based treatment. Additionally, the modified intent-to-treat population included 1291 patients, of whom 641 were included in the 6-month group and 650 in the 3-month group. In the 6-month group, 23% of patients subsequently experienced recurrence vs 22% in the 3-month group. The median follow-up was 74.7 months.

In the 3-month group, the 5-year disease-free survival (DFS) was 75.2% (95% CI, 71.7%-78.4%) and 74.2% (95% CI, 70.6%-77.5%) in the 6-month group (HR, 0.95; 95% CI, 0.77-1.18; P = .64). Those who received mFOLFOX6, the 5-year DFS rate was 68.6% (95% CI, 60.8%-75.1%) vs 69.7% (95% CI, 61.8%-76.2%) in the 3-month and 6-month groups, respectively (HR, 1.04; 95% CI, 0.71-1.54; P = .82). For those who received CAPOX, the 5-year DFS was 77.4% (95% CI, 73.4%-80.9%) vs 75.8% (95% CI, 71.6%-79.4%) in the 3- and 6-month groups, respectively (HR, 0.91; 95% CI, 0.71-1.18; P = .49).

At 5-years, the DFS for those with low-risk disease in the 3-month group was 86.5% (95% CI, 82.5%-89.7%) compared with 84.8% (95% CI, 80.6%-88.2%) in the 6-month group (HR, 0.85; 95% CI, 0.59-1.23; P = .39). Those with high-risk disease in the 3-month group had DFS rates of 60.7% (95% CI, 54.8%-66.2%) vs 61.5% (95% CI, 55.6%-66.9%) in the 6-month group (HR, 1.04; 95% CI, 0.80-1.35; P = .75).

Patients who had low-risk disease and were treated with mFOLFOX6 for 3 months appeared to have worse outcomes than those treated for 6 months (HR, 1.41; 95% CI, 0.68-2.91; P = .35). However, those in the same risk group who received 3 months of CAPOX appeared to have better outcomes than those who received treatment for 6 months (HR, 0.70; 95% CI, 0.45-1.09; P = .11). Those with high-risk disease had similar outcomes when treated with mFOLFOC6 (HR, 1.01; 95% CI, 0.63-1.60; P = .98) and CAPOX (HR, 1.07; 95% CI, 0.78-1.46; P = .70) for 3 and 6 months, respectively.

For patients with low-risk disease, the 5-year OS in the 3-month group was 92.7% (95% CI, 89.5%-95.0%) and 91.8% (95% CI, 88.4%-94.3%) in the 6-month group (HR, 0.86; 95% CI, 0.53-1.37; P = .52). Those with high-risk disease in the 3-month treatment group, had OS rates of 79.8% (95% CI, 74.6%-84.0%) vs 79.8% (95% CI, 74.7%-84.1%) in the 6-month group (HR, 0.96; 95% CI, 0.68-1.35; P = .82).

Additionally, findings from an OS analysis indicated that those with low-risk disease receiving 3 months of mFOLFOX6 had worse outcomes than those receiving treatment at 6 months (HR, 1.26; 95% CI, 0.54-2.94; P = .60). Conversely, those receiving CAPOX for 3 months in the same risk group had better outcomes than 6 months (HR, 0.71; 95% CI, 0.40-1.26; P = .24). For those with high-risk disease, treatment for 3 and 6 months resulted in similar outcomes for both 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).

A post hoc analysis showed the most common areas of recurrence were in the liver (31%), lung (30%), peritoneum (23%), and lymph node (22%). Those who received treatment for 6-months more commonly had recurrence in the liver (P = .0017), and recurrence in the lung was more common in the 3-month group (P = .0075). Investigators did not find a significant difference in area of recurrence between the mFOLFOX6 and CAPOX arms.

Seventy-three percent of patients in the 3-month treatment group and 82% in the 6-month group experienced PSN of any grade (OR, 0.589; 95% CI, 0.451-0.768; P <.0001). Grade 2 or 3 PSN occurred in 13% and 1% of patients in the 3-month group, respectively, and in 30% and 6% of those in the 6-month group (OR, 0.281; 95% CI, 0.214-0.370; P <.0001).

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. Published Online May 5, 2022. doi:10.1200/JCO.21.02628

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