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

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 ColoteChristophe Tournigand, Christophe Louvet, Alex Duval, Jean François Fléjou, Aimery De Gramont

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)4176-4187
Number of pages12
JournalJournal of Clinical Oncology
Volume33
Issue number35
DOIs
Publication statusPublished - Dec 10 2015

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oxaliplatin
DNA Mismatch Repair
Leucovorin
Fluorouracil
Colonic Neoplasms
Mutation
Survival
Disease-Free Survival
Adjuvant Chemotherapy
Paraffin
Formaldehyde
Multicenter Studies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / André, Thierry; De Gramont, Armand; Vernerey, Dewi; Chibaudel, Benoist; Bonnetain, Franck; Tijeras-Raballand, Annemilaï; Scriva, Aurelie; Hickish, Tamas; Tabernero, Josep; Van Laethem, Jean Luc; Banzi, Maria; Maartense, Eduard; Shmueli, Einat; Carlsson, Goran U.; Scheithauer, Werner; Papamichael, Demetris; Möehler, Marcus; Landolfi, Stefania; Demetter, Pieter; Colote, Soudhir; Tournigand, Christophe; Louvet, Christophe; Duval, Alex; Fléjou, Jean François; De Gramont, Aimery.

In: Journal of Clinical Oncology, Vol. 33, No. 35, 10.12.2015, p. 4176-4187.

Research output: Contribution to journalArticle

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 2015, '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 of Clinical Oncology, vol. 33, no. 35, pp. 4176-4187. https://doi.org/10.1200/JCO.2015.63.4238
André, Thierry ; De Gramont, Armand ; Vernerey, Dewi ; Chibaudel, Benoist ; Bonnetain, Franck ; Tijeras-Raballand, Annemilaï ; Scriva, Aurelie ; Hickish, Tamas ; Tabernero, Josep ; Van Laethem, Jean Luc ; Banzi, Maria ; Maartense, Eduard ; Shmueli, Einat ; Carlsson, Goran U. ; Scheithauer, Werner ; Papamichael, Demetris ; Möehler, Marcus ; Landolfi, Stefania ; Demetter, Pieter ; Colote, Soudhir ; Tournigand, Christophe ; Louvet, Christophe ; Duval, Alex ; Fléjou, Jean François ; De Gramont, Aimery. / 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. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 35. pp. 4176-4187.
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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",
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.",
author = "Thierry Andr{\'e} and {De Gramont}, Armand and Dewi Vernerey and Benoist Chibaudel and Franck Bonnetain and Annemila{\"i} Tijeras-Raballand and Aurelie Scriva and Tamas Hickish and Josep Tabernero and {Van Laethem}, {Jean Luc} and Maria Banzi and Eduard Maartense and Einat Shmueli and Carlsson, {Goran U.} and Werner Scheithauer and Demetris Papamichael and Marcus M{\"o}ehler and Stefania Landolfi and Pieter Demetter and Soudhir Colote and Christophe Tournigand and Christophe Louvet and Alex Duval and Fl{\'e}jou, {Jean Fran{\cc}ois} and {De Gramont}, Aimery",
year = "2015",
month = "12",
day = "10",
doi = "10.1200/JCO.2015.63.4238",
language = "English",
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pages = "4176--4187",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
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TY - JOUR

T1 - Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer

T2 - Updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study

AU - André, Thierry

AU - De Gramont, Armand

AU - Vernerey, Dewi

AU - Chibaudel, Benoist

AU - Bonnetain, Franck

AU - Tijeras-Raballand, Annemilaï

AU - Scriva, Aurelie

AU - Hickish, Tamas

AU - Tabernero, Josep

AU - Van Laethem, Jean Luc

AU - Banzi, Maria

AU - Maartense, Eduard

AU - Shmueli, Einat

AU - Carlsson, Goran U.

AU - Scheithauer, Werner

AU - Papamichael, Demetris

AU - Möehler, Marcus

AU - Landolfi, Stefania

AU - Demetter, Pieter

AU - Colote, Soudhir

AU - Tournigand, Christophe

AU - Louvet, Christophe

AU - Duval, Alex

AU - Fléjou, Jean François

AU - De Gramont, Aimery

PY - 2015/12/10

Y1 - 2015/12/10

N2 - 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.

AB - 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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