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.

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.

• Authors: 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 Colote, Christophe Tournigand, Christophe Louvet, Alex Duval, Jean-François Fléjou, Aimery de Gramont
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 35 Pg. 4176-87 (Dec 10 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26527776 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Organoplatinum Compounds
• Glutamic Acid
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Valine
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Chemotherapy, Adjuvant
• Colonic Neoplasms (drug therapy, genetics, mortality, pathology)
• 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