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Medline ® Abstract for Reference 46

of 'Adjuvant therapy for resected stage III (node-positive) colon cancer'

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.
AndréT, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, Scriva A, Hickish T, Tabernero J, Van Laethem JL, Banzi M, Maartense E, Shmueli E, Carlsson GU, Scheithauer W, Papamichael D, Möehler M, Landolfi S, Demetter P, Colote S, Tournigand C, Louvet C, Duval A, Fléjou JF, de Gramont A
J Clin Oncol. 2015 Dec;33(35):4176-87. Epub 2015 Nov 2.
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.
Thierry Andréand Jean-François Fléjou, Hôpital St Antoine; Thierry Andréand Jean-François Fléjou, University Pierre et Marie Curie Paris VI; Thierry André, Benoist Chibaudel, AnnemilaïTijeras-Raballand, Soudhir Colote, and Aimery de Gramont, Groupe Coopérateur Multdisciplinaire en Ocologie (GERCOR) Oncology Multidisciplinary Group and GERCOR-Innovative Research Consortium; Christophe Louvet, Institut Mutualiste Montsouris; Alex Duval, L'Institut National de la Santéet de la Recherche Médicale UMRS 938, Paris; Armand de Gramont, Benoist Chibaudel, Annemilaï, Tijeras Raballand, Aurelie Scriva, and Aimery de Gramont, Institut Hospitalier Franco Britannique, Levallois-Perret; Dewi Vernerey and Franck Bonnetain, Hôpital Saint-Jacques, Besançon; Christophe Tournigand, Hôpital Henri Mondor, Créteil, France; Armand de Gramont, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Tamas Hickish, Dorset Bournemouth University, Dorset, United Kingdom; Josep Tabernero and Stefania Landolfi, Vall d'Hebron University Hospital and Institute of Oncology, Barcelona; Josep Tabernero, TTD Group, Madrid, Spain; Jean Luc Van Laethem and Pieter Demetter, Hôpital Universitaire Erasme, Brussels, Belgium; Maria Banzi, Arcispedale Santa Maria Nuova, Reggio, Italy; Eduard Maartense, Reinier de Graaf Groep, Delft, the Netherlands; Einat Shmueli, Sheba Medical Center, Tel Hashomer, Israel; Goran U. Carlsson, Sahlgrenska University Hospital,Östra, Sweden; Werner Scheithauer, Medical University of Vienna, Vienna, Austria; Demetris Papamichael, B.O. Cyprus Oncology Centre, Nicosia, Cyprus; and Marcus Möehler, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany. thierry.andre@aphp.fr.