Final Results of NO16968 Trial Show Improved Overall Survival With Adjuvant XELOX vs Bolus 5-FU/Leucovorin in Stage III Colon Cancer
As reported by Schmoll et al in the Journal of Clinical Oncology, the final results of the phase III NO16968 trial showed that adjuvant therapy with XELOX (capecitabine, oxaliplatin) improved overall survival vs fluorouracil (5-FU)/leucovorin in patients with resected stage III colon cancer. Biomarker analysis indicated that low tumor expression of dihydropyrimidine dehydrogenase was predictive of greater XELOX efficacy. The initial report from the trial showed that disease-free survival, the primary endpoint, was significantly improved with XELOX.
In this open-label trial, 1,886 patients from 226 sites in 29 countries were randomly assigned between April 2003 and October 2004 to receive XELOX (n = 944) or Mayo Clinic or Roswell Park bolus 5-FU/leucovorin regimens (n = 942).
Improved Overall Survival
Seven-year disease-free survival was 63% in the XELOX group vs 56% in the 5-FU/leucovorin group (hazard ratio [HR] = 0.80, P = .004), and 7-year overall survival was 73% vs 67% (HR = 0.83, P = .04). A total of 68% and 77% of patients with relapsed or new colorectal cancer received drug treatment for metastatic disease, including irinotecan (54% and 46%), oxaliplatin (18% and 58%), bevacizumab (Avastin; 23% and 23%), and cetuximab (Erbitux; 17% and 15%).
Biomarker Analysis
Biomarker analysis in 242 XELOX patients and 256 5-FU/leucovorin patients showed that low vs high tumor expression of dihydropyrimidine dehydrogenase was associated with better outcome in XELOX patients; hazard ratios for high vs low levels were 2.45 (P < .001) for disease-free survival and 2.75 (P < .001) for overall survival. No significant associations were observed between tumor biomarkers and outcomes in 5-FU/leucovorin patients.
The investigators concluded: “XELOX improved [overall survival] compared with bolus [5-FU/leucovorin] in patients with resected stage III colon cancer after a median follow-up of almost 7 years. XELOX should be considered a standard adjuvant treatment option in patients with stage III disease. Tumoral dihydropyrimidine dehydrogenase expression is a promising predictive, and potentially, highly clinically relevant, biomarker for XELOX efficacy requiring further prospective evaluation.”
Hans-Joachim Schmoll, MD, of Martin-Luther-Universitat, Halle, Germany, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by F. Hoffmann-La Roche. For full disclosures of the study authors, visit jco.ascopubs.org.
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