XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results

• Published in: British journal of cancer 2011-06, Vol.105 (1), p.58-64
• Main Authors: Cassidy, J, Clarke, S, Díaz-Rubio, E, Scheithauer, W, Figer, A, Wong, R, Koski, S, Rittweger, K, Gilberg, F, Saltz, L
• Format: Article
• Language: English
• Subjects: 692/699/67/1059/99; 692/699/67/1504/1885; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical Study; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug Resistance; Epidemiology; Female; Fluorouracil - analogs & derivatives; Fluorouracil - therapeutic use; Follow-Up Studies; Humans; Leucovorin - therapeutic use; Liver Neoplasms - drug therapy; Liver Neoplasms - secondary; Male; Middle Aged; Molecular Medicine; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Oncology; Organoplatinum Compounds - therapeutic use; Survival Rate; Treatment Outcome; Young Adult
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.201

Background: We report updated overall survival (OS) data from study NO16966, which compared capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX4) as first-line therapy in metastatic colorectal cancer. Methods: NO16966 was a randomised, two-arm, non-inferiority, phase III comparison of XELOX vs FOLFOX4, which was subsequently amended to a 2 × 2 factorial design with further randomisation to bevacizumab or placebo. A planned follow-up exploratory analysis of OS was performed. Results: The intent-to-treat (ITT) population comprised 2034 patients (two-arm portion, n =634; 2 × 2 factorial portion, n =1400). For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms (hazard ratio 0.95 (97.5% CI 0.85–1.06)). In the pooled XELOX/XELOX-placebo arms, median OS was 19.0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms (hazard ratio 0.95 (97.5% CI 0.83–1.09)). FOLFOX4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhoea and grade 3 hand-foot syndrome than FOLFOX4. Conclusion: Updated survival data from study NO16966 show that XELOX is similar to FOLFOX4, confirming the primary analysis of progression-free survival. XELOX can be considered as a routine first-line treatment option for patients with metastatic colorectal cancer.