In a Korean phase III noninferiority trial (KCSG CO09-07) reported in the Journal of Clinical Oncology, Kim et al found noninferiority in disease-free survival and reduced risk of neuropathy for adjuvant therapy with 3 vs 6 months of oxaliplatin plus 6 months of fluoropyrimidine treatment in high-risk stage II or stage III colorectal cancer. Noninferiority was driven by outcomes in patients with stage III disease who received capecitabine.
As stated by the investigators, “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…. The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified.”
Study Details
In the open-label multicenter trial, 1,788 patients were randomly assigned between January 2010 and January 2016 to receive oxaliplatin for 3 months (n = 893) or 6 months (n = 895) in combination with 6 months of fluoropyrimidine treatment. The 3-month group consisted of 196 patients with high-risk stage II disease and 697 with stage III disease; the 6-month group included 196 and 699, respectively.
Patients with high-risk stage II disease could receive only fluorouracil/leucovorin (as modified FOLFOX6 when given with oxaliplatin), whereas patients with stage III disease could receive investigator choice of fluorouracil/leucovorin or capecitabine (as CAPOX when given with oxaliplatin). Overall, fluoropyrimidine treatment consisted of fluorouracil/leucovorin in 620 patients in the 3-month group and 617 in the 6-month group and capecitabine in 273 and 278, respectively. The primary endpoint was disease-free survival; the noninferiority threshold was an upper 95% confidence interval (CI) limit of 1.25 for the hazard ratio (HR) for 3 vs 6 months.
Key Findings
Disease-free survival at 3 years was 84.7% (95% CI = 82.2%–87.0%) in the 3-month group vs 83.7% (95% CI = 81.1%-86.0%) in the 6-month group (HR = 0.953, 95% CI = 0.769–1.180; P = .0065 for noninferiority).
Analysis among subgroups showed that noninferiority was not established for 3 vs 6 months among patients with high-risk stage II disease (HR = 1.192, 95% CI = 0.698–2.036; P = .4313 for noninferiority) or among patients with high-risk stage II or stage III disease receiving fluorouracil/leucovorin (HR = 1.102, 95% CI = 0.847–1.435; P = .2164 for noninferiority). Noninferiority of 3 months vs 6 months was established among patients with stage III disease who received capecitabine (HR = 0.713, 95% CI = 0.530–0.959; P = .0009 for noninferiority).
Neuropathy of any grade was observed in 69.5% of the 6-month group vs 58.3% of the 3-month group (P < .0001). Grade ≥ 2 neuropathy occurred in 25.5% (grade 3 or 4 in 3.6%) vs 14.1% (grade 3 in 2.4%).
The investigators concluded: “This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III [colorectal cancer].”
Young Suk Park, MD, PhD, of Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Colorectal Cancer Committee of the Korean Cancer Study Group and Sanofi-Aventis. For full disclosures of the study authors, visit ascopubs.org.
