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

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 upda...

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Veröffentlicht in:Journal of clinical oncology 2015-12, Vol.33 (35), p.4176-4187
Hauptverfasser: 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
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container_end_page 4187
container_issue 35
container_start_page 4176
container_title Journal of clinical oncology
container_volume 33
creator 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
description 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. 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. 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. 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.
doi_str_mv 10.1200/jco.2015.63.4238
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This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. 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. 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. 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. 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This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. 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. 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. 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.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Chemotherapy, Adjuvant</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - mortality</subject><subject>Colonic Neoplasms - pathology</subject><subject>Disease-Free Survival</subject><subject>DNA Mismatch Repair</subject><subject>Female</subject><subject>Fluorouracil - administration &amp; dosage</subject><subject>Follow-Up Studies</subject><subject>Glutamic Acid</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Injections, Intravenous</subject><subject>Kaplan-Meier Estimate</subject><subject>Leucovorin - administration &amp; 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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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-7aa2e88af625fe29474a7d5447d84cc269c6b8bafb362db6694ce084f35092a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration &amp; dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Chemotherapy, Adjuvant</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - mortality</topic><topic>Colonic Neoplasms - pathology</topic><topic>Disease-Free Survival</topic><topic>DNA Mismatch Repair</topic><topic>Female</topic><topic>Fluorouracil - administration &amp; 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This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. 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. 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. 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.</abstract><cop>United States</cop><pmid>26527776</pmid><doi>10.1200/jco.2015.63.4238</doi><tpages>12</tpages></addata></record>
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subjects Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Chemotherapy, Adjuvant
Colonic Neoplasms - drug therapy
Colonic Neoplasms - genetics
Colonic Neoplasms - mortality
Colonic Neoplasms - pathology
Disease-Free Survival
DNA Mismatch Repair
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
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
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