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.

Details

Serval ID
serval:BIB_3C369D0ABBAB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Author(s)
André T., de Gramont A., Vernerey D., Chibaudel B., Bonnetain F., Tijeras-Raballand A., Scriva A., Hickish T., Tabernero J., Van Laethem J.L., Banzi M., Maartense E., Shmueli E., Carlsson G.U., Scheithauer W., Papamichael D., Möehler M., Landolfi S., Demetter P., Colote S., Tournigand C., Louvet C., Duval A., Fléjou J.F., de Gramont A.
ISSN
1527-7755 (Electronic)
ISSN-L
0732-183X
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
33
Number
35
Pages
4176-4187
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Chemotherapy, Adjuvant, Colonic Neoplasms/drug therapy, Colonic Neoplasms/genetics, DNA Mismatch Repair, Disease-Free Survival, Female, Fluorouracil/administration & dosage, Follow-Up Studies, Glutamic Acid, Humans, Infusions, Intravenous, Injections, Intravenous, Kaplan-Meier Estimate, Leucovorin/administration & dosage, Male, Middle Aged, Mutation, Neoplasm Staging, Odds Ratio, Organoplatinum Compounds/administration & dosage, Prognosis, Proto-Oncogene Proteins B-raf/genetics, Treatment Outcome, Valine
Pubmed
Web of science
Create date
10/01/2016 15:28
Last modification date
20/08/2019 13:32
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