G. Bruera, E. Ricevuto, G. Masi, F. Loupakis, and L. Salvatore, Intensive chemotherapy of metastatic colorectal cancer: weighing between safety and clinical efficacy Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial, Evaluation of Lancet Oncol Expert Opin Biol Ther, vol.11, issue.11, pp.845-52821, 2010.

E. Van-cutsem, C. Kohne, E. Hitre, J. Zaluski, C. Chien et al., Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer, New England Journal of Medicine, vol.360, issue.14, pp.1408-1417, 2009.
DOI : 10.1056/NEJMoa0805019

C. Bokemeyer, I. Bondarenko, A. Makhson, J. Hartmann, J. Aparicio et al., Fluorouracil, Leucovorin, and Oxaliplatin With and Without Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer, Journal of Clinical Oncology, vol.27, issue.5, pp.663-671, 2009.
DOI : 10.1200/JCO.2008.20.8397

W. Ince, A. Jubb, S. Holden, E. Holmgren, P. Tobin et al., Association of k-ras, b-raf, and p53 Status With the Treatment Effect of Bevacizumab, JNCI Journal of the National Cancer Institute, vol.97, issue.13, pp.981-989, 2005.
DOI : 10.1093/jnci/dji174

H. Hurwitz, Y. J. Ince, W. Novotny, W. Rosen, and O. , The Clinical Benefit of Bevacizumab in Metastatic Colorectal Cancer Is Independent of K-ras Mutation Status: Analysis of a Phase III Study of Bevacizumab with Chemotherapy in Previously Untreated Metastatic Colorectal Cancer, The Oncologist, vol.14, issue.1, pp.22-28, 2009.
DOI : 10.1634/theoncologist.2008-0213

G. Folprecht, T. Gruenberger, W. Bechstein, H. Raab, F. Lordick et al., Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial, The Lancet Oncology, vol.11, issue.1, pp.38-47, 2010.
DOI : 10.1016/S1470-2045(09)70330-4

G. Bruera, A. Santomaggio, K. Cannita, L. Baldi, P. Tudini et al., "Poker" association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study, BMC Cancer, vol.28, issue.13, p.567, 2010.
DOI : 10.1016/S0140-6736(00)02528-9

G. Masi, F. Loupakis, L. Salvatore, L. Fornaro, C. Cremolini et al., Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial, The Lancet Oncology, vol.11, issue.9, pp.845-852, 2010.
DOI : 10.1016/S1470-2045(10)70175-3

C. Garufi, A. Torsello, S. Tumolo, G. Ettorre, M. Zeuli et al., Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadiuvant chemotherapy in colorectal liver metastases

G. Masi, E. Vasile, F. Loupakis, S. Cupini, L. Fornaro et al., Randomized Trial of Two Induction Chemotherapy Regimens in Metastatic Colorectal Cancer: An Updated Analysis, JNCI Journal of the National Cancer Institute, vol.103, issue.1, pp.21-30, 2011.
DOI : 10.1093/jnci/djq456

G. Bruera, K. Cannita, F. Giuliante, L. Baldi, P. Vicentini et al., Effectiveness of Liver Metastasectomies in Patients With Metastatic Colorectal Cancer Treated With FIr-B/FOx Triplet Chemotherapy Plus Bevacizumab, Clinical Colorectal Cancer, vol.11, issue.2, pp.119-126, 2012.
DOI : 10.1016/j.clcc.2011.11.002

C. Ficorella, G. Bruera, K. Cannita, G. Porzio, L. Baldi et al., Triplet Chemotherapy in Patients With Metastatic Colorectal Cancer: Toward the Best Way to Safely Administer a Highly Active Regimen in Clinical Practice, Clinical Colorectal Cancer, vol.11, issue.4, pp.229-237, 2012.
DOI : 10.1016/j.clcc.2012.05.001

G. Bruera, K. Cannita, D. Giacomo, D. Lamy, A. Troncone et al., Prognostic value of KRAS genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease, BMC Medicine, vol.60, issue.1, p.135, 2012.
DOI : 10.1016/S1470-2045(09)70330-4

URL : https://hal.archives-ouvertes.fr/inserm-00764322

S. Forbes, J. Clements, E. Dawson, S. Bamford, T. Webb et al., COSMIC 2005, British Journal of Cancer, vol.57, issue.2, pp.318-322, 2005.
DOI : 10.1126/science.1096096

O. Donoghue, D. Giaretti, W. Rapallo, A. Russo, A. Bazan et al., Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study, Br J Cancer, vol.85, pp.692-696, 2001.

N. Normanno, S. Tejpar, F. Morbillo, D. Luca, A. Van-cutsem et al., Implications for KRAS status and EGFR-targeted therapies in metastatic CRC, Nature Reviews Clinical Oncology, vol.276, issue.9, pp.519-527, 2009.
DOI : 10.1038/nrclinonc.2009.111

S. Schubbert, K. Shannon, and G. Bollag, Hyperactive Ras in developmental disorders and cancer, Nature Reviews Cancer, vol.91, issue.4, pp.295-308, 2007.
DOI : 10.1038/nrc2109

S. Guerrero, I. Casanova, L. Farrè, A. Mazo, G. Capellà et al., K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression, Cancer Res, vol.60, pp.6750-6756, 2000.

J. Bos, D. Toksoz, C. Marshall, M. Verlaan-de-vries, G. Veeneman et al., Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia, Nature, vol.12, issue.6022, pp.726-730, 1985.
DOI : 10.1038/315726a0

H. Andreyev, A. Norman, D. Cunningham, J. Oates, and P. Clarke, Kirsten ras Mutations in Patients With Colorectal Cancer: the Multicenter "RASCAL" Study, JNCI Journal of the National Cancer Institute, vol.90, issue.9, pp.675-684, 1998.
DOI : 10.1093/jnci/90.9.675

W. Samowitz, K. Curtin, D. Schaffer, M. Robertson, M. Leppert et al., Relationship of Ki-ras mutations in colon cancers to tumor location, stage, and survival: a population-based study, Cancer Epidemiol Biomarkers Prev, vol.9, pp.1193-1197, 2000.

J. Westra, M. Schaapveld, H. Hollema, J. De-boer, M. Kraak et al., Mutation Is More Relevant Than Microsatellite Instability Status for the Prediction of Disease-Free Survival in Adjuvant-Treated Stage III Colon Cancer Patients, Journal of Clinical Oncology, vol.23, issue.24, pp.5635-5643, 2005.
DOI : 10.1200/JCO.2005.04.096

D. Fiore, F. Blanchard, F. Charbonnier, F. , L. Pessot et al., Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy, British Journal of Cancer, vol.14, issue.8, pp.1166-1169, 2007.
DOI : 10.1093/jnci/92.3.205

A. Lamy, F. Blanchard, L. Pessot, F. Sesboué, R. et al., Metastatic colorectal cancer KRAS genotyping in routine practice: results and pitfalls, Modern Pathology, vol.46, issue.8, pp.1090-1100, 2011.
DOI : 10.1038/modpathol.2011.60

P. Therasse, S. Arbuck, E. Eisenhauer, J. Wanders, R. Kaplan et al., New Guidelines to Evaluate the Response to Treatment in Solid Tumors, JNCI: Journal of the National Cancer Institute, vol.92, issue.3, pp.205-216, 2000.
DOI : 10.1093/jnci/92.3.205

E. Kaplan and P. Meier, Nonparametric Estimation from Incomplete Observations, Journal of the American Statistical Association, vol.37, issue.282, pp.457-481, 1958.
DOI : 10.1214/aoms/1177731566

R. Peto and J. Peto, Asymptotically Efficient Rank Invariant Test Procedures, Journal of the Royal Statistical Society. Series A (General), vol.135, issue.2, pp.185-206, 1972.
DOI : 10.2307/2344317

Y. Imamura, T. Morikawa, X. Liao, P. Lochhead, A. Kuchiba et al., Specific Mutations in KRAS Codons 12 and 13, and Patient Prognosis in 1075 BRAF Wild-Type Colorectal Cancers, Clinical Cancer Research, vol.18, issue.17, pp.4753-4763, 2012.
DOI : 10.1158/1078-0432.CCR-11-3210

D. Nicolantonio, F. Martini, M. Molinari, F. Sartore-bianchi, A. Arena et al., Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer, Journal of Clinical Oncology, vol.26, issue.35, pp.5705-5712, 2008.
DOI : 10.1200/JCO.2008.18.0786

E. Van-cutsem, C. Köhne, I. Làng, G. Folprecht, M. Nowacki et al., Mutation Status, Journal of Clinical Oncology, vol.29, issue.15, pp.2011-2019, 2011.
DOI : 10.1200/JCO.2010.33.5091

C. Bokemeyer, I. Bondarenko, J. Hartmann, F. De-braud, G. Schuch et al., Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study, Annals of Oncology, vol.22, issue.7, pp.1535-1546, 2011.
DOI : 10.1093/annonc/mdq632

S. Tejpar, I. Celik, M. Schlichting, U. Sartorius, C. Bokemeyer et al., G13D Tumor Mutations With Outcome in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy With or Without Cetuximab, Journal of Clinical Oncology, vol.30, issue.29, pp.3570-3577, 2012.
DOI : 10.1200/JCO.2012.42.2592

W. De-roock, D. Jonker, D. Nicolantonio, F. Sartore-bianchi, A. Tu et al., Association of KRAS p.G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With Cetuximab, JAMA, vol.304, issue.16, pp.1812-1820, 2010.
DOI : 10.1001/jama.2010.1535

C. Mao, Y. Huang, Z. Yang, D. Zheng, J. Chen et al., p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer, Cancer, vol.5, issue.4, pp.714-721, 2013.
DOI : 10.1002/cncr.27804

URL : https://hal.archives-ouvertes.fr/in2p3-00010893

J. Chen, Y. Ye, H. Sun, and G. Shi, Association between KRAS codon 13 mutations and clinical response to anti-EGFR treatment in patients with metastatic colorectal cancer: results from a meta-analysis, Cancer Chemotherapy and Pharmacology, vol.2, issue.1, pp.265-272, 2013.
DOI : 10.1007/s00280-012-2005-9

M. Peeters, J. Douillard, E. Van-cutsem, S. Siena, K. Zhang et al., Codon 12 and 13 Alleles in Patients With Metastatic Colorectal Cancer: Assessment As Prognostic and Predictive Biomarkers of Response to Panitumumab, Journal of Clinical Oncology, vol.31, issue.6, pp.759-765, 2013.
DOI : 10.1200/JCO.2012.45.1492