After curative-intent surgery, patients with stage III colon cancer who received oxaliplatin plus capecitabine (XELOX) had improved disease-free survival and overall survival, compared with those who received fluorouracil/folinic acid (FU/FA), according to secondary analysis of the NO16968 study.
After a median 74-month follow-up, 320 of 944 patients in the XELOX group (34%) experienced relapse, developed a new colon cancer, or died, compared with 379 of 942 patients in the FU/FA group (40%), for a hazard ratio of 0.80 (95% confidence interval, 0.69-0.93; P = .004). After a median follow-up of 83 months, 242 (26%) in the XELOX group died, compared with 286 (30%) in the FU/FA group, for a HR of 0.83 (95% CI, 0.70-0.99; P = .04).
Disease-free survival (DFS) and overall survival (OS) rates were consistently higher for XELOX after 3-7 years of follow-up, and the differences between the treatments increased after the primary analysis. Survival rates for XELOX and FU/FA were 86% vs. 84%, respectively, in year 3; 80% vs. 78% in year 4; 77% vs. 74% in year 5; 76% vs. 71% in year 6; and 73% vs. 67% in year 7.
“Multiple incremental advances in the treatment and detection of recurrent colon cancer mean that a longer follow-up of 6 or 7 years may be required to assess survival benefit in modern adjuvant trials reliably,” wrote Dr. Hans-Joachim Schmoll of the department of oncology/hematology at Martin Luther University in Halle, Germany, and his colleagues (J Clin Oncol. 2015 Aug 31. doi: 10.1200/JCO.2014.60.9107).
The survival benefits observed in this trial are in line with those of the previous MOSAIC trial, which used a similar cumulative dose of oxaliplatin (1,040 mg/m2 and 1,020 mg/m2, respectively).
“Together, these trials show that oxaliplatin improves OS when added to a fluoropyrimidine as adjuvant therapy in patients with stage III colon cancer, and that the fluoropyrimidine may be delivered intravenously by infusion or orally for the same result,” the investigators observed.
The multinational, open-label, parallel, randomized phase III study included 1,886 patients who received XELOX or FU/FA from 2003 to 2004.
Subset analysis for patients older than 70 years showed an increased survival benefit for XELOX over FU/FA, but the effect size was smaller than in younger patients and the conclusions were not definitive because of the small subgroup sizes.
A biomarker analysis included 26% of the trial participants: 242 in the XELOX group and 256 in the FU/FA group. Patients in the XELOX group who had lower expression of dihydropyrimidine dehydrogenase had better outcomes (P less than 001). Patients in the FU/FA group showed no significant associations between tumor biomarkers and outcomes. The study was supported by F. Hoffmann-La Roche. Dr. Schmoll reported consulting or advisory roles with Genentech, Taiho Pharmaceutical, and Bayer Schering Pharma. Several of his coauthors reported ties to industry sources.