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 |
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| 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 |
| format | Article |
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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><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/jco.2015.63.4238</identifier><identifier>PMID: 26527776</identifier><language>eng</language><publisher>United States</publisher><subject>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</subject><ispartof>Journal of clinical oncology, 2015-12, Vol.33 (35), p.4176-4187</ispartof><rights>2015 by American Society of Clinical Oncology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-7aa2e88af625fe29474a7d5447d84cc269c6b8bafb362db6694ce084f35092a33</citedby><cites>FETCH-LOGICAL-c412t-7aa2e88af625fe29474a7d5447d84cc269c6b8bafb362db6694ce084f35092a33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3731,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26527776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>André, Thierry</creatorcontrib><creatorcontrib>de Gramont, Armand</creatorcontrib><creatorcontrib>Vernerey, Dewi</creatorcontrib><creatorcontrib>Chibaudel, Benoist</creatorcontrib><creatorcontrib>Bonnetain, Franck</creatorcontrib><creatorcontrib>Tijeras-Raballand, Annemilaï</creatorcontrib><creatorcontrib>Scriva, Aurelie</creatorcontrib><creatorcontrib>Hickish, Tamas</creatorcontrib><creatorcontrib>Tabernero, Josep</creatorcontrib><creatorcontrib>Van Laethem, Jean Luc</creatorcontrib><creatorcontrib>Banzi, Maria</creatorcontrib><creatorcontrib>Maartense, Eduard</creatorcontrib><creatorcontrib>Shmueli, Einat</creatorcontrib><creatorcontrib>Carlsson, Goran U</creatorcontrib><creatorcontrib>Scheithauer, Werner</creatorcontrib><creatorcontrib>Papamichael, Demetris</creatorcontrib><creatorcontrib>Möehler, Marcus</creatorcontrib><creatorcontrib>Landolfi, Stefania</creatorcontrib><creatorcontrib>Demetter, Pieter</creatorcontrib><creatorcontrib>Colote, Soudhir</creatorcontrib><creatorcontrib>Tournigand, Christophe</creatorcontrib><creatorcontrib>Louvet, Christophe</creatorcontrib><creatorcontrib>Duval, Alex</creatorcontrib><creatorcontrib>Fléjou, Jean-François</creatorcontrib><creatorcontrib>de Gramont, Aimery</creatorcontrib><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</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><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.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & 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 & 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 & dosage</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Staging</subject><subject>Odds Ratio</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Treatment Outcome</subject><subject>Valine</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kUuL1EAUhQtRnHZ070pq6WLS1itVaXcx2BrppmHaAV2Fm0plJk2SivVonN_nHzOhR-FyL1zO-c7iIPSWkjVlhHw4abtmhKZrydeC8ewZWtGUqUSpNH2OVkRxltCM_7hCr7w_EUJFxtOX6IrJWaWUXKE_eXOKZxgD3vbROhsd6K6_wTsTtT1b1403GMYGH35D3009hG7E8xwD3BtcljjYeZe4sL0dcQGjNu4jvpsaCKbBlCQ_DTh8jO7cnaG_kGLQdjAe51pb13Tj_QL5dJtv8T6GOWAGLbp95wcI-gHfmgk6t0SG6LFtcXgweH845mUxP2Pz-Bq9aKH35s3TvUZ328_fi6_J7vClLPJdogVlIVEAzGQZtJKlrWEboQSoJhVCNZnQmsmNlnVWQ1tzyZpayo3QhmSi5SnZMOD8Gr2_cCdnf0XjQzV0Xpu-h9HY6CuqhOJEUSlmKblItbPeO9NWk-sGcI8VJdVSXfWtOFRLdZXk1VLdbHn3RI_1YJr_hn9d8b_HTJVF</recordid><startdate>20151210</startdate><enddate>20151210</enddate><creator>André, Thierry</creator><creator>de Gramont, Armand</creator><creator>Vernerey, Dewi</creator><creator>Chibaudel, Benoist</creator><creator>Bonnetain, Franck</creator><creator>Tijeras-Raballand, Annemilaï</creator><creator>Scriva, Aurelie</creator><creator>Hickish, Tamas</creator><creator>Tabernero, Josep</creator><creator>Van Laethem, Jean Luc</creator><creator>Banzi, Maria</creator><creator>Maartense, Eduard</creator><creator>Shmueli, Einat</creator><creator>Carlsson, Goran U</creator><creator>Scheithauer, Werner</creator><creator>Papamichael, Demetris</creator><creator>Möehler, Marcus</creator><creator>Landolfi, Stefania</creator><creator>Demetter, Pieter</creator><creator>Colote, Soudhir</creator><creator>Tournigand, Christophe</creator><creator>Louvet, Christophe</creator><creator>Duval, Alex</creator><creator>Fléjou, Jean-François</creator><creator>de Gramont, Aimery</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20151210</creationdate><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</title><author>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</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 - 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Academic</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>André, Thierry</au><au>de Gramont, Armand</au><au>Vernerey, Dewi</au><au>Chibaudel, Benoist</au><au>Bonnetain, Franck</au><au>Tijeras-Raballand, Annemilaï</au><au>Scriva, Aurelie</au><au>Hickish, Tamas</au><au>Tabernero, Josep</au><au>Van Laethem, Jean Luc</au><au>Banzi, Maria</au><au>Maartense, Eduard</au><au>Shmueli, Einat</au><au>Carlsson, Goran U</au><au>Scheithauer, Werner</au><au>Papamichael, Demetris</au><au>Möehler, Marcus</au><au>Landolfi, Stefania</au><au>Demetter, Pieter</au><au>Colote, Soudhir</au><au>Tournigand, Christophe</au><au>Louvet, Christophe</au><au>Duval, Alex</au><au>Fléjou, Jean-François</au><au>de Gramont, Aimery</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2015-12-10</date><risdate>2015</risdate><volume>33</volume><issue>35</issue><spage>4176</spage><epage>4187</epage><pages>4176-4187</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>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.</abstract><cop>United States</cop><pmid>26527776</pmid><doi>10.1200/jco.2015.63.4238</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0732-183X |
| ispartof | Journal of clinical oncology, 2015-12, Vol.33 (35), p.4176-4187 |
| issn | 0732-183X 1527-7755 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1747307164 |
| source | MEDLINE; American Society of Clinical Oncology Online Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-06T11%3A29%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adjuvant%20Fluorouracil,%20Leucovorin,%20and%20Oxaliplatin%20in%20Stage%20II%20to%20III%20Colon%20Cancer:%20Updated%2010-Year%20Survival%20and%20Outcomes%20According%20to%20BRAF%20Mutation%20and%20Mismatch%20Repair%20Status%20of%20the%20MOSAIC%20Study&rft.jtitle=Journal%20of%20clinical%20oncology&rft.au=Andr%C3%A9,%20Thierry&rft.date=2015-12-10&rft.volume=33&rft.issue=35&rft.spage=4176&rft.epage=4187&rft.pages=4176-4187&rft.issn=0732-183X&rft.eissn=1527-7755&rft_id=info:doi/10.1200/jco.2015.63.4238&rft_dat=%3Cproquest_cross%3E1747307164%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1747307164&rft_id=info:pmid/26527776&rfr_iscdi=true |