Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: Updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study

Thierry André*, Armand De Gramont, Dewi Vernerey, Benoist Chibaudel, Franck Bonnetain, Annemilaï Tijeras-Raballand, Aurelie Scriva, Tamas Hickish, Josep Tabernero, Jean Luc Van Laethem, Maria Banzi, Eduard Maartense, Einat Shmueli, Goran U. Carlsson, Werner Scheithauer, Demetris Papamichael, Marcus Möehler, Stefania Landolfi, Pieter Demetter, Soudhir ColoteChristophe Tournigand, Christophe Louvet, Alex Duval, Jean François Fléjou, Aimery De Gramont

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. Methods: Survival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens. Results: After a median follow-up of 9.5 years, 10-year OS rates in the bolus/infusional fluorouracil plus leucovorin (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX4) arms were 67.1% versus 71.7% (hazard ratio [HR], 0.85; P = .043) in the whole population, 79.5% versus 78.4% for stage II (HR, 1.00; P = .980), and 59.0% versus 67.1% for stage III (HR, 0.80; P = .016) disease. Ninety-five patients (9.4%) had MMR-deficient (dMMR) tumors, and 94 (10.4%) had BRAF mutation. BRAF mutation was not prognostic for OS (P = .965), but dMMR was an independent prognostic factor (HR, 2.02; 95% CI, 1.15 to 3.55; P = .014). HRs for DFS and OS benefit in the FOLFOX4 arm were 0.48 (95% CI, 0.20 to 1.12) and 0.41 (95% CI, 0.16 to 1.07), respectively, in patients with stage II to III dMMR and 0.50 (95% CI, 0.25 to 1.00) and 0.66 (95% CI, 0.31 to 1.42), respectively, in those with BRAF mutation. Conclusion: The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with dMMR or BRAF mutation.

Original languageEnglish
Pages (from-to)4176-4187
Number of pages12
JournalJournal of Clinical Oncology
Volume33
Issue number35
DOIs
StatePublished - 10 Dec 2015
Externally publishedYes

Funding

FundersFunder number
Aberdeen Royal Infirmary
Arcispedale Santa Maria Nuova
Bristol Oncology and Hematology Centre
Cancer Research United Kingdom
Clinique de Courlancy
Cliniques Universitaires UCL Mont-Godinne
F.G. de Braud
Hospital Universitario Clínico San Carlos
Karolinska Hospital
National Cancer Institute Istituto di Ricovero e Cura a Carattere Scientifico Bari
North Middlesex Hospital, London
Nottingham City Hospital
Orbis Medical Centre
Princess Alexandra Hospital
Royal Bournemouth Hospital
Royal Marsden Hospital
Royal Surrey County Hospital
St John Hospital
St Vincent’s Catholic Medical Center
Univ.-Klink für Innere Medizin
University College of London Cancer Institute
Istituto Europeo di Oncologia
Semmelweis Egyetem
Cliniques Universitaires Saint-Luc

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