Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07

Abstract

Purpose: The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified.

Patients and methods: This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25.

Results: In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven.

Conclusion: This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).

Conflict of interest statement

Yeul Hong Kim

Stock and Other Ownership Interests: OncoMaster

Research Funding: MSD Oncology (Inst), Ono Pharmaceutical (Inst), Macrogenics (Inst), Korea Astellas (Inst), Zymeworks (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.

CONSORT diagram. ITT, intention-to-treat; PPA, per-protocol population analysis.

FIG 2.

DFS by study group. DFS, disease-free survival; HR, hazard ratio.

FIG 3.

DFS by study group, stage group, and regimen: (A) stage II high risk, (B) stage III low risk, (C) stage III high risk, (D) CAPOX, and (E) FOLFOX. CAPOX, capecitabine plus oxaliplatin; DFS, disease-free survival; FOLFOX, infusional fluorouracil, leucovorin, and oxaliplatin; HR, hazard ratio.

FIG 4.

Forest plot for disease-free survival. FOLFOX, infusional fluorouracil, leucovorin, and oxaliplatin; CAPOX, capecitabine plus oxaliplatin; Het, heterogeneity; HR, hazard ratio; N, node; T, tumor.

FIG 5.

OS by study group. HR, hazard ratio; OS, overall survival.

FIG A1.

Comparison of DFS in the 3-month arm with that of patients in the 6-month arm who received oxaliplatin of at least 5 months. DFS, disease-free survival; HR, hazard ratio.