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

被引：612

作者：

Andre, Thierry ^{[1
,2
,3
,4
]}

de Gramont, Armand ^{[7
,10
]}

Vernerey, Dewi ^{[8
]}

Chibaudel, Benoist ^{[3
,4
,7
]}

Bonnetain, Franck ^{[8
]}

Tijeras-Raballand, Annemilai ^{[3
,4
,7
]}

Scriva, Aurelie ^{[7
]}

Hickish, Tamas ^{[11
]}

Tabernero, Josep ^{[12
,13
,14
]}

Van Laethem, Jean Luc ^{[15
]}

Banzi, Maria ^{[16
]}

Maartense, Eduard ^{[17
]}

Shmueli, Einat ^{[18
]}

Carlsson, Goran U. ^{[19
]}

Scheithauer, Werner ^{[20
]}

Papamichael, Demetris ^{[21
]}

Moeehler, Marcus ^{[22
]}

Landolfi, Stefania ^{[12
,13
]}

Demetter, Pieter ^{[15
]}

Colote, Soudhir ^{[3
,4
]}

Tournigand, Christophe ^{[9
]}

Louvet, Christophe ^{[5
]}

Duval, Alex ^{[6
]}

Flejou, Jean-Francois ^{[1
,2
]}

de Gramont, Aimery ^{[3
,4
,7
]}

机构：

[1] Hop St Antoine, F-75012 Paris, France

[2] Univ Paris 06, Paris, France

[3] Oncol Multidisciplinary Grp, Groupe Cooperateur Multdisciplinaire Ocol GERCOR, Paris, France

[4] GERCOR Innovat Res Consortium, Paris, France

[5] Inst Mutualiste Montsouris, Paris, France

[6] Inst Natl Sante & Rech Med, Paris, France

[7] Inst Hosp Franco Britann, Levallois Perret, France

[8] Hop St Jacques, F-25030 Besancon, France

[9] Hop Henri Mondor, F-94010 Creteil, France

[10] CHU Vaudois, CH-1011 Lausanne, Switzerland

[11] Dorset Bournemouth Univ, Bournemouth, Dorset, England

[12] Vall dHebron Univ Hosp, Barcelona, Spain

[13] Inst Oncol, Barcelona, Spain

[14] TTD Grp, Madrid, Spain

[15] Hop Univ Erasme, Brussels, Belgium

[16] Arcispedale Santa Maria Nuova, Reggio, Italy

[17] Reinier Graaf Grp, Delft, Netherlands

[18] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel

[19] Sahlgrens Univ Hosp, Ostra, Sweden

[20] Med Univ Vienna, Vienna, Austria

[21] BO Cyprus Oncol Ctr, Nicosia, Cyprus

[22] Johannes Gutenberg Univ Mainz, Univ Med Ctr, D-55122 Mainz, Germany

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 35期

关键词：

METASTATIC COLORECTAL-CANCER; DISEASE-FREE SURVIVAL; MICROSATELLITE-INSTABILITY; NSABP C-07; FOLLOW-UP; TRIAL; CHEMOTHERAPY; THERAPY; IMPACT;

D O I：

10.1200/JCO.2015.63.4238

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2015 by American Society of Clinical Oncology

引用

页码：4176 / +

页数：14

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