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
| Autor: | Soudhir Colote, Demetris Papamichael, Josep Tabernero, Maria Banzi, Armand de Gramont, Aimery de Gramont, Franck Bonnetain, Alex Duval, Benoist Chibaudel, E. Maartense, Thierry André, Jean-Luc Van Laethem, Pieter Demetter, Dewi Vernerey, Göran Carlsson, Marcus Möehler, Einat Shacham Shmueli, Christophe Louvet, Werner Scheithauer, Aurelie Scriva, Tamas Hickish, Jean François Fléjou, Christophe Tournigand, Annemilaï Tijeras-Raballand, Stefania Landolfi |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf Oncology Cancer Research medicine.medical_specialty Organoplatinum Compounds Colorectal cancer medicine.medical_treatment Population Leucovorin Glutamic Acid Kaplan-Meier Estimate DNA Mismatch Repair Disease-Free Survival Internal medicine Antineoplastic Combined Chemotherapy Protocols Odds Ratio medicine Humans Stage (cooking) Infusions Intravenous education Aged Neoplasm Staging education.field_of_study Chemotherapy business.industry Hazard ratio Valine Middle Aged Prognosis medicine.disease digestive system diseases Surgery Oxaliplatin Treatment Outcome Chemotherapy Adjuvant Fluorouracil Colonic Neoplasms Injections Intravenous Mutation Female business Adjuvant Follow-Up Studies medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 33:4176-4187 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2015.63.4238 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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