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Thématique :
- Cancer colorectal (CCR)
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Immédiatement
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Nom du veilleur :
Professeur Astrid LIÈVRE
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Journal of clinical oncology (JCO)
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2016/01
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2015 Dec 10;33(35):4176-87
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doi: 10.1200/JCO.2015.63.4238. Epub 2015 Nov 2.
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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.
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André T, 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
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http://www.ncbi.nlm.nih.gov/pubmed/?term=Adjuvant+Fluorouracil%2C+Leucovorin%2C+and+Oxaliplatin+in+Stage+II+to+III+Colon+Cancer%3A+Updated+10-Year+Survival+and+Outcomes+According+to+BRAF+Mutation+and+Mismatch+Repair+Status+of+the+MOSAIC+Study.
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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.
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Résultats à 10 ans et selon le statut MSI et BRAF de l’essai MOSAIC qui démontrait la supériorité du FOLFOX sur le LV5FU2 en adjuvant des cancers coliques opérés de stade II-III
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Confirmation du bénéfice en survie globale à 10 ans du FOLFOX, observé uniquement pour les tumeurs de stade III (pas les stades II).
Aucune valeur pronostique de la mutation de BRAF, alors que le statut MSI était un facteur indépendant de bon pronostic.
Bénéfice du FOLFOX maintenu en cas de statut MSI et de mutation de BRAF (tendance non significative).
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Le FOLFOX confirme à long terme sa supériorité par rapport au LV5FU2 et semble apporter également un bénéfice en présence d’un statut MSI ou d’une mutation de BRAF.
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