F. Bray, A. Jemal, N. Grey, J. Ferlay, and D. Forman, Global cancer transitions according to the Human Development Index (2008-2030): a population-based study, Lancet Oncol, vol.13, pp.70211-70216, 2012.

L. A. Torre, F. Bray, R. L. Siegel, J. Ferlay, J. Lortet-tieulent et al., Global cancer statistics, CA Cancer J Clin, vol.65, pp.87-108, 2012.
DOI : 10.3322/caac.21262

URL : https://onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21262

R. L. Siegel, K. D. Miller, and A. Jemal, Cancer statistics, CA Cancer J Clin, vol.66, pp.7-30, 2016.
DOI : 10.3322/caac.21254

URL : https://onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21254

N. Howlader, A. Noone, M. Krapcho, D. Miller, K. Bishop et al., SEER cancer statistics review, pp.1975-2013, 2017.

D. Rio, M. Mollevi, C. Vezzio-vie, N. Bibeau, F. Ychou et al., Specific extracellular matrix remodeling signature of colon hepatic metastases, PLoS One, vol.8, 2013.

E. Van-cutsem, A. Cervantes, R. Adam, A. Sobrero, J. H. Van-krieken et al., ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, Ann Oncol, vol.27, pp.1386-422, 2016.

D. Papamichael, R. Audisio, B. Glimelius, A. De-gramont, G. et al., Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013, Ann Oncol, vol.26, pp.463-76, 2015.

L. Talarico, G. Chen, and R. Pazdur, Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration

, J Clin Oncol, vol.22, pp.4626-4657, 2004.

J. H. Lewis, M. L. Kilgore, D. P. Goldman, E. L. Trimble, R. Kaplan et al., Participation of patients 65 years of age or older in cancer clinical trials, J Clin Oncol, vol.21, pp.1383-1392, 2003.

M. Oken, R. Creech, D. Tormey, J. Horton, T. Davis et al., Toxicity and response criteria of the Eastern Cooperative Oncology Group, Am J Clin Oncol, vol.5, pp.649-55, 1982.

J. Bennouna, J. Sastre, D. Arnold, P. Österlund, R. Greil et al., Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial, Lancet Oncol, vol.14, pp.29-37, 2013.

C. Bokemeyer, I. Bondarenko, J. T. 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, Ann Oncol, vol.22, pp.1535-1581, 2011.

M. Borner, D. Koeberle, V. Moos, R. Saletti, P. Rauch et al., Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK, Ann Oncol, vol.19, pp.1288-92, 2008.

T. Brodowicz, T. E. Ciuleanu, D. Radosavljevic, E. Shacham-shmueli, D. Vrbanec et al., FOLFOX4 plus cetuximab administered weekly or every second week in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer: a randomized phase II CECOG study, Ann Oncol, vol.24, pp.1769-77, 2013.

J. Cassidy, S. Clarke, E. Diaz-rubio, W. Scheithauer, A. Figer et al., XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results, Br J Cancer, vol.105, pp.58-64, 2011.

D. Cunningham, Y. Humblet, S. Siena, D. Khayat, H. Bleiberg et al., Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer, N Engl J Med, vol.351, pp.337-382, 2004.

D. Cunningham, I. Lang, E. Marcuello, V. Lorusso, J. Ocvirk et al., Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial, Lancet Oncol, vol.14, issue.13, pp.70154-70156, 2013.

E. Diaz-rubio, A. Gomez-espana, B. Massuti, J. Sastre, A. Abad et al., Firstline XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study, Oncologist, vol.17, pp.15-25, 2012.

E. Dotan, N. J. Meropol, B. Burtness, C. S. Denlinger, J. Lee et al., A phase II study of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as frontline therapy for metastatic colorectal cancer. A Fox Chase extramural research study, J Gastrointest Cancer, vol.43, pp.562-571, 2012.

J. Y. Douillard, S. Siena, J. Cassidy, J. Tabernero, R. Burkes et al., Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer, Ann Oncol, vol.25, pp.1346-55, 2014.

J. Y. Douillard, T. Zemelka, G. Fountzilas, C. Barone, M. Schlichting et al., FOLFOX4 with cetuximab vs. UFOX with cetuximab as first-line therapy in metastatic colorectal cancer: the randomized phase II FUTURE study, Clin Colorectal Cancer, vol.13, pp.14-26, 2014.

M. Ducreux, A. Adenis, J. Pignon, E. François, B. Chauffert et al., Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: final results from a randomised phase II study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan (FNCLCC ACCORD 13/0503 study), Eur J Cancer, vol.49, pp.1236-1281, 2013.

G. Folprecht, T. Gruenberger, W. Bechstein, H. R. Raab, J. Weitz et al., Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study), Ann Oncol, vol.25, pp.1018-1043, 2014.

C. S. Fuchs, J. Marshall, E. Mitchell, R. Wierzbicki, V. Ganju et al., Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in firstline treatment of metastatic colorectal cancer: results from the BICC-C study, J Clin Oncol, vol.25, pp.4779-86, 2007.

K. M. Galal, M. Abdelsalam, E. E. Fawzy, S. Mansour, K. Zaghloul et al., Role of bevacizumab as post-progression maintenance therapy in metastatic colon cancer

, J Med Sci, vol.8, pp.452-60, 2008.

B. J. Giantonio, P. J. Catalano, N. J. Meropol, O. Dwyer, P. J. Mitchell et al., Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200, J Clin Oncol, vol.25, pp.1539-1583, 2007.

A. Grothey, E. Van-cutsem, A. Sobrero, S. Siena, A. Falcone et al., Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial, Lancet, vol.381, pp.303-315, 2013.

Z. Guan, J. Xu, R. Luo, F. Feng, L. Wang et al., Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III artist trial, Chin J Cancer, vol.30, pp.682-691, 2011.

J. R. Hecht, E. Mitchell, T. Chidiac, C. Scroggin, C. Hagenstad et al., A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer, J Clin Oncol, vol.27, pp.672-80, 2009.

V. Heinemann, L. F. Von-weikersthal, T. Decker, A. Kiani, U. Vehling-kaiser et al., FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial, Lancet Oncol, vol.15, pp.1065-75, 2014.

H. S. Hochster, L. L. Hart, R. K. Ramanathan, B. H. Childs, J. D. Hainsworth et al., Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE study, J Clin Oncol, vol.26, pp.3523-3532, 2008.

H. Hurwitz, L. Fehrenbacher, W. Novotny, T. Cartwright, J. Hainsworth et al., Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N Engl J Med, vol.350, pp.2335-2377, 2004.

H. Hurwitz, E. P. Mitchell, T. Cartwright, A. Kwok, S. Hu et al., A randomized, phase II trial of standard triweekly compared with dose-dense biweekly capecitabine plus oxaliplatin plus bevacizumab as first-line treatment for metastatic colorectal cancer: XELOX-A-DVS (dense versus standard), Oncologist, vol.17, pp.937-983, 2012.

D. J. Jonker, C. J. O'callaghan, C. S. Karapetis, J. R. Zalcberg, D. Tu et al., Cetuximab for the treatment of colorectal cancer, N Engl J Med, vol.357, pp.2040-2048, 2007.

F. Kabbinavar, H. I. Hurwitz, L. Fehrenbacher, N. J. Meropol, W. F. Novotny et al., Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/ leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer, J Clin Oncol, vol.21, pp.60-65, 2003.

F. F. Kabbinavar, J. Schulz, M. Mccleod, T. Patel, J. T. Hamm et al., Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial, J Clin Oncol, vol.23, pp.3697-705, 2005.

S. Kato, H. Andoh, M. Gamoh, T. Yamaguchi, Y. Murakawa et al., Safety verification trials of mFOLFIRI and sequential IRIS + bevacizumab as first-or second-line therapies for metastatic colorectal cancer in Japanese patients, Oncology, vol.83, pp.101-108, 2012.

N. E. Kemeny, W. R. Jarnagin, M. Capanu, Y. Fong, A. N. Gewirtz et al., Randomized phase II trial of adjuvant hepatic arterial infusion and systemic chemotherapy with or without bevacizumab in patients with resected hepatic metastases from colorectal cancer, J Clin Oncol, vol.29, pp.884-893, 2011.

F. Loupakis, C. Cremolini, G. Masi, S. Lonardi, V. Zagonel et al., Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer, N Engl J Med, vol.371, pp.1609-1627, 2014.

S. Madajewicz, D. M. Waterhouse, P. S. Ritch, M. Q. Khan, D. J. Higby et al., randomized phase II trial of bevacizumab plus folinic acid, fluorouracil, gemcitabine (FFG) versus bevacizumab plus folinic acid, fluorouracil, oxaliplatin (FOLFOX4) as first-line therapy for patients with advanced colorectal cancer, Invest New Drugs, vol.30, pp.772-780, 2012.

T. S. Maughan, R. A. Adams, C. G. Smith, A. M. Meade, M. T. Seymour et al., Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial, Lancet, vol.377, pp.2103-2117, 2011.

N. Moosmann, V. Weikersthal, L. F. Vehling-kaiser, U. Stauch, M. Hass et al., Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104 -a randomized trial of the German AIO CRC study group, J Clin Oncol, vol.29, pp.1050-1058, 2011.

J. Ocvirk, T. Brodowicz, F. Wrba, T. E. Ciuleanu, G. Kurteva et al., Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial, World J Gastroenterol, vol.16, pp.3133-3176, 2010.

M. Peeters, T. J. Price, A. Cervantes, A. F. Sobrero, M. Ducreux et al., Final results from a randomized phase 3 study of FOLFIRI {+/?} panitumumab for second-line treatment of metastatic colorectal cancer, Ann Oncol, vol.25, pp.107-123, 2014.

T. J. Price, M. Peeters, T. W. Kim, J. Li, S. Cascinu et al., Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, noninferiority phase 3 study, Lancet Oncol, vol.15, issue.14, pp.70118-70122, 2014.

J. Primrose, S. Falk, M. Finch-jones, J. Valle, D. O'reilly et al., Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the new EPOC randomised controlled trial, Lancet Oncol, vol.15, pp.601-612, 2014.

L. Saltz, S. Badarinath, S. Dakhil, B. Bienvenu, W. G. Harker et al., Phase III trial of cetuximab, bevacizumab, and 5-fluorouracil/leucovorin vs. FOLFOXbevacizumab in colorectal cancer, Clin Colorectal Cancer, vol.11, pp.101-112, 2012.
DOI : 10.1016/j.clcc.2011.05.006

L. B. Saltz, H. J. Lenz, H. L. Kindler, H. S. Hochster, S. Wadler et al., Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study, J Clin Oncol, vol.25, pp.4557-61, 2007.

W. Schmiegel, A. Reinacher-schick, D. Arnold, S. Kubicka, W. Freier et al.,

, Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group, Ann Oncol, vol.24, pp.1580-1587, 2013.

L. S. Schwartzberg, F. Rivera, M. Karthaus, G. Fasola, J. L. Canon et al., PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer, J Clin Oncol, vol.32, pp.2240-2247, 2014.

M. T. Seymour, S. R. Brown, G. Middleton, T. Maughan, S. Richman et al., Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wildtype, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial, Lancet Oncol, vol.14, pp.749-59, 2013.
DOI : 10.1016/s1470-2045(13)70163-3

URL : https://doi.org/10.1016/s1470-2045(13)70163-3

A. F. Sobrero, J. Maurel, L. Fehrenbacher, W. Scheithauer, Y. A. Abubakr et al., EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer, J Clin Oncol, vol.26, pp.2311-2320, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00484211

J. Souglakos, N. Ziras, S. Kakolyris, I. Boukovinas, N. Kentepozidis et al., Randomised phase-II trial of CAPIRI (capecitabine, irinotecan) plus bevacizumab vs FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) plus bevacizumab as first-line treatment of patients with unresectable/metastatic colorectal cancer (mCRC), Br J Cancer, vol.106, pp.453-462, 2012.

G. P. Stathopoulos, C. Batziou, D. Trafalis, J. Koutantos, S. Batzios et al., Treatment of colorectal cancer with and without bevacizumab: a phase III study, Oncology, vol.78, pp.376-81, 2010.

N. C. Tebbutt, K. Wilson, V. J. Gebski, M. M. Cummins, D. Zannino et al., Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group randomized phase III MAX study, J Clin Oncol, vol.28, pp.3191-3199, 2010.

J. Tol, M. Koopman, A. Cats, C. J. Rodenburg, G. Creemers et al., Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer, N Engl J Med, vol.360, pp.563-72, 2009.
DOI : 10.1056/nejmoa0808268

URL : https://pure.uva.nl/ws/files/822115/78787_321888.pdf

K. M. Tveit, T. Guren, B. Glimelius, P. Pfeiffer, H. Sorbye et al., Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study, J Clin Oncol, vol.30, pp.1755-62, 2012.

E. Van-cutsem, C. H. Köhne, E. Hitre, J. Zaluski, C. Chien et al., Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer, N Engl J Med, vol.360, pp.1408-1425, 2009.

E. Van-cutsem, M. Peeters, S. Siena, Y. Humblet, A. Hendlisz et al., Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy -refractory metastatic colorectal cancer, J Clin Oncol, vol.25, pp.1658-64, 2007.

E. Van-cutsem, J. Tabernero, R. Lakomy, H. Prenen, J. Prausová et al., Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen, J Clin Oncol, vol.30, pp.3499-506, 2012.

H. Wasan, A. M. Meade, R. Adams, R. Wilson, C. Pugh et al., Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial, Lancet Oncol, vol.15, issue.14, pp.70106-70114, 2014.

S. Yalcin, R. Uslu, F. Dane, U. Yilmaz, N. Zengin et al., Bevacizumab + capecitabine as maintenance therapy after initial bevacizumab + XELOX treatment in previously untreated patients with metastatic colorectal cancer: phase III "Stop and Go" study results-a Turkish Oncology Group Trial, Oncology, vol.85, pp.328-363, 2013.

Y. Yamada, D. Takahari, H. Matsumoto, H. Baba, M. Nakamura et al., Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial, Lancet Oncol, vol.14, pp.1278-86, 2013.

L. C. Ye, T. S. Liu, L. Ren, Y. Wei, D. X. Zhu et al., Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases, J Clin Oncol, vol.31, pp.1931-1939, 2013.

, Harmonisation of technical requirements for registration of pharmaceuticals for human use, Studies in support of special populations: geriatrics E7, 1993.

R. Jennens, G. Giles, and R. Fox, Increasing underrepresentation of elderly patients with advanced colorectal or non-small-cell lung cancer in chemotherapy trials, Intern Med J, vol.36, pp.216-236, 2006.

A. Fourrier-réglat, D. Smith, M. Rouyer, J. Bénichou, R. Guimbaud et al., Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort, Target Oncol, vol.9, pp.311-320, 2014.

M. Rouyer, A. Fourrier-réglat, D. Smith, Y. Becouarn, R. Guimbaud et al., Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: results of the ETNA observational cohort

, J Geriatr Oncol, vol.7, pp.187-94, 2016.

V. Shankaran, D. Mummy, L. Koepl, A. Bansal, D. K. Mirick et al., Survival and lifetime costs associated with first-line bevacizumab use in older patients with metastatic colorectal cancer, Oncologist, vol.19, pp.892-901, 2014.

H. Tsai, J. Marshall, S. Weiss, C. Huang, J. Warren et al., Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study, Ann Oncol, vol.24, pp.1574-1583, 2013.

S. Parakh, H. Wong, R. Rai, S. Ali, K. Field et al., Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia, J Geriatr Oncol, vol.6, pp.387-94, 2015.

P. Ward, J. R. Hecht, H. J. Wang, R. Dichmann, A. Liem et al., Physical function and quality of life in frail and/or elderly patients with metastatic colorectal cancer treated with capecitabine and bevacizumab: an exploratory analysis, J Geriatr Oncol, vol.5, pp.368-75, 2014.

H. Sorbye, P. Pfeiffer, N. Cavalli-björkman, C. Qvortrup, M. H. Holsen et al., Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients, Cancer, vol.115, pp.4679-87, 2009.

T. Asmis, E. Powell, C. Karapetis, D. Jonker, D. Tu et al., age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)-results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care, Ann Oncol, vol.22, pp.118-144, 2011.

N. A. Jackson, J. Barrueco, R. Soufi-mahjoubi, J. Marshall, E. Mitchell et al., Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study, Cancer, vol.115, pp.2617-2646, 2009.

T. J. Price, D. Zannino, K. Wilson, R. Simes, J. Cassidy et al., Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised

R. A. Adams, A. M. Meade, A. Madi, D. Fisher, E. Kay et al., Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience, Br J Cancer, vol.100, pp.251-259, 2009.

R. G. Amado, M. Wolf, M. Peeters, E. Van-cutsem, S. Siena et al., Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer, J Clin Oncol, vol.26, pp.1626-1660, 2008.

T. Asmis, E. Powell, C. Karapetis, D. Jonker, D. Tu et al., age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care, Ann Oncol, vol.22, pp.118-144, 2011.

D. O. Bates, P. J. Catalano, K. E. Symonds, A. H. Varey, P. Ramani et al., Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab, Clin Cancer Res, vol.18, pp.6384-91, 2012.

A. Bethke, K. Kuhne, I. Platzek, and C. Stroszczynski, Neoadjuvant treatment of colorectal liver metastases is associated with altered contrast enhancement on computed tomography, Cancer Imaging, vol.11, pp.91-100, 2011.

C. Bokemeyer, I. Bondarenko, A. Makhson, J. T. Hartmann, J. Aparicio et al., Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer, J Clin Oncol, vol.27, pp.663-71, 2009.

M. A. Bruhn, A. R. Townsend, K. Lee, C. Shivasami, A. Price et al., Proangiogenic tumor proteins as potential predictive or prognostic biomarkers for bevacizumab therapy in metastatic colorectal cancer, Int J Cancer, vol.135, pp.731-772, 2014.

H. E. Carter, D. Zannino, J. Simes, R. Schofield, D. J. Howard et al., The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study, Eur J Cancer, vol.50, pp.535-578, 2014.

M. T. De-bruijn, D. A. Raats, J. Tol, J. Hinrichs, S. Teerenstra et al., Combined KRAS and TP53 mutation status is not predictive in CAPOX-treated metastatic colorectal cancer, Anticancer Res, vol.31, pp.1379-85, 2011.

J. Douillard, K. Oliner, S. Siena, J. Tabernero, R. Burkes et al., Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer, N Engl J Med, vol.369, pp.1023-1057, 2013.

J. Douillard, S. Siena, J. Cassidy, J. Tabernero, R. Burkes et al., Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study, J Clin Oncol, vol.28, pp.4697-705, 2010.

G. Folprecht, T. Gruenberger, W. O. 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, Lancet Oncol, vol.11, pp.38-47, 2010.

C. T. Harbison, C. E. Horak, J. M. Ledeine, P. Mukhopadhyay, D. P. Malone et al., Validation of companion diagnostic for detection of mutations in codons 12 and 13 of the KRAS gene in patients with metastatic colorectal cancer: analysis of the NCIC CTG CO.17 trial, Arch Pathol Lab Med, vol.137, pp.820-827, 2013.

H. I. Hurwitz, J. Yi, W. Ince, W. F. Novotny, and O. Rosen, 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, pp.22-30, 2009.

H. I. Hurwitz, L. Fehrenbacher, J. D. Hainsworth, W. Heim, J. Berlin et al., Bevacizumab in combination with fluorouracil and leucovorin: An active regimen for first-line metastatic colorectal cancer, J Clin Oncol, vol.23, pp.3502-3510, 2005.

N. A. Jackson, J. Barrueco, R. Soufi-mahjoubi, J. Marshall, E. Mitchell et al., Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: Findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study, Cancer, vol.115, pp.2617-2646, 2009.

C. Karapetis, D. Jonker, O. 'callaghan, and C. , Cetuximab plus BSC versus BSC alone in the treatment of metastatic EGFR-positive colorectal cancer, Signal, vol.6, pp.15-22, 2005.

C. Morris, J. Jurgensmeier, and J. Robertson, AZD2171, an oral, highly potent, and reversible inhibitor of VEGFR, signaling with potential for the treatment of advanced colorectal cancer, J Clin Oncol, 2006.

M. Peeters, T. J. Price, and Y. S. Hotko, Randomized phase III study of panitumumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): patient-reported outcomes (PRO), J Clin Oncol, p.282, 2010.

H. Zheng, J. Z. Chen, W. J. Liao, and R. C. Luo, Efficacy of Avastin in combination with irinotecan for metastatic colorectal cancer. Nan Fang Yi Ke Xue Xue Bao, vol.26, pp.689-91, 2006.

. Calgb/swog-c80405, A phase III trial of FOLFIRI or FOLFOX with bevacizumab or cetuximab or both for untreated metastatic adenocarcinoma of the colon or rectum, Clin Adv Hematol Oncol, vol.4, pp.452-455, 2006.

, Panitumumab with FOLFOX4 compared to FOLFOX4 alone as first-line treatment in metastatic colorectal cancer, Clin Adv Hematol Oncol, vol.8, pp.9-10, 2010.

, Pflege Z, vol.66, p.252, 2013.

, Multikinase inhibitor regorafenib offers an efficient therapeutic alternative, Rev Med Suisse, vol.10, p.1108, 2014.

D. Barnett, A. Stevens, and C. Longson, Appraisal of bevacizumab and cetuximab for treatment of metastatic colorectal cancer in the UK, Lancet Oncol, vol.7, pp.807-815, 2006.

E. Grothey and E. Chu, The clinical efficacy of FOLFIRI and bevacizumab in combination as first-line therapy of metastatic colorectal cancer, Clin Colorectal Cancer, vol.6, pp.621-625, 2007.

F. Kabbinavar, C. Irl, A. Zurlo, and H. Hurwitz, Bevacizumab improves the overall and progression-free survival of patients with metastatic colorectal cancer treated with 5-fluorouracil-based regimens irrespective of baseline risk, Oncology, vol.75, pp.215-238, 2008.

S. London, Regorafenib prolongs survival after failed therapies, Oncol Rep, p.11, 2012.

N. Osterweil, Second-line bevacizumab adds weeks in metastatic CRC, Oncol Rep, p.10, 2012.

N. Price, Bevacizumab improves the efficacy of 5-fluorouracil/leucovorin in patients with advanced colorectal cancer, Clin Colorectal Cancer, vol.4, pp.89-91, 2004.

W. Scheithauer and W. Schmiegel, Bevacizumab plus Oxaliplatin-Based Regimens for the Treatment of Colorectal Cancer, Onkologie, vol.32, pp.431-440, 2009.

, Adding a humanized antibody to vascular endothelial growth factor (Bevacizumab, Avastin) to chemotherapy improves survival in metastatic colorectal cancer, Clin Colorectal Cancer, vol.3, pp.85-93, 2003.

, Phase III aflibercept-chemotherapy combination trial shows benefit in previously treated metastatic colorectal cancer patients, Oncol Williston Park, vol.25, p.1213, 2011.

, Cetuximab plus FOLFIRI in first-line treatment of KRAS mutation-negative, EGFR-positive metastatic colorectal cancer, Community Oncol, vol.9, pp.304-310, 2012.

C. Giessen, L. F. Von-weikersthal, A. Hinke, S. Stintzing, F. Kullmann et al., A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: the AIO KRK 0110 trial/ML22011 trial, BMC Cancer, vol.11, p.367, 2011.

J. R. Hecht and A. L. Cohn, SPIRITT: A study of second-line treatment of metastatic colorectal cancer with FOLFIRI plus panitumumab or bevacizumab, Community Oncol, vol.5, pp.1-4, 2008.

H. Mishima, K. Oba, J. Sakamoto, K. Muro, T. Yoshino et al., FOLFIRI plus bevacizumab 5 mg/kg versus 10 mg/kg as second-line therapy in patients with metastatic colorectal cancer who have failed firstline bevacizumab plus oxaliplatin-based therapy: A randomized phase III study (EAGLE study), Jpn J Clin Oncol, vol.42, pp.134-142, 2012.

N. Snoeren, E. E. Voest, A. M. Bergman, O. Dalesio, H. M. Verheul et al., A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment, BMC Cancer, vol.10, p.545, 2010.

A. P. Venook, C. D. Blanke, D. Niedzwiecki, H. J. Lenz, J. R. Taylor et al., Cancer and Leukemia Group B/Southwest Oncology Group trial 80405: a phase III trial of chemotherapy and biologics for patients with untreated advanced colorectal adenocarcinoma, Clin Colorectal Cancer, vol.5, pp.292-296, 2005.

A. P. Venook, C. D. Blanke, D. Niedzwiecki, H. Lenz, J. R. Taylor et al., Revisiting the Cancer and Leukemia Group B/Southwest Oncology Group 80405 trial: A phase III trial of chemotherapy and biologic agents for patients with untreated advanced colorectal adenocarcinoma, Clin Colorectal Cancer, vol.6, pp.536-544, 2007.

H. Wasan, R. A. Adams, R. H. Wilson, C. A. Pugh, D. Fisher et al., Intermittent Chemotherapy (CT) Plus Continuous or Intermittent Cetuximab I in the First-line Treatment of Advanced Colorectal Cancer (aCRC): Results of the Two-arm Phase II Randomised MRC COIN-B Trial, Eur J Cancer, vol.47, issue.1, p.6006, 2011.

S. Yalcin, R. Uslu, F. Dane, U. Yilmaz, N. Zengin et al., A randomized, multicenter phase III trial of bevacizumab plus capecitabine as maintenance treatment after initial treatment with bevacizumab plus XELOX in previously untreated metastatic colorectal cancer, J Clin Oncol, vol.29, 2011.

S. Yalcin, R. Uslu, F. Dane, U. Yilmaz, N. Zengin et al., Bevacizumab plus capecitabine as maintenance treatment after initial treatment with bevacizumab plus XELOX in previously untreated metastatic colorectal cancer: Updated findings from a randomized, multicenter phase III trial, J Clin Oncol, vol.29, p.3579, 2011.

, Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): A randomized phase III trial, Oncologie, vol.15, pp.271-275, 2013.

F. Kabbinavar, H. I. Hurwitz, L. Fehrenbacher, N. J. Meropol, W. F. Novotny et al., Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer, J Clin Oncol, vol.21, pp.60-65, 2003.

D. Cunningham, Y. Humblet, S. Siena, D. Khayat, H. Bleiberg et al., Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer, N Engl J Med, vol.351, pp.337-382, 2004.

H. Hurwitz, L. Fehrenbacher, W. Novotny, T. Cartwright, J. Hainsworth et al., Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N Engl J Med, vol.350, pp.2335-2377, 2004.

F. F. Kabbinavar, J. Schulz, M. Mccleod, T. Patel, J. T. Hamm et al., Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: Results of a randomized phase II trial, J Clin Oncol, vol.23, pp.3697-705, 2005.

C. S. Fuchs, J. Marshall, E. Mitchell, R. Wierzbicki, V. Ganju et al., Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C study, J Clin Oncol, vol.25, pp.4779-86, 2007.

B. J. Giantonio, P. J. Catalano, N. J. Meropol, O. Dwyer, P. J. Mitchell et al., Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200, J Clin Oncol, vol.25, pp.1539-1583, 2007.

D. J. Jonker, C. J. O'callaghan, C. S. Karapetis, J. R. Zalcberg, D. Tu et al., Cetuximab for the treatment of colorectal cancer, N Engl J Med, vol.357, pp.2040-2048, 2007.

L. B. Saltz, H. Lenz, H. L. Kindler, H. S. Hochster, S. Wadler et al., Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecanrefractory colorectal cancer: The BOND-2 study, J Clin Oncol, vol.25, pp.4557-61, 2007.

E. Van-cutsem, M. Peeters, S. Siena, Y. Humblet, A. Hendlisz et al., Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer, J Clin Oncol, vol.25, pp.1658-64, 2007.

M. Borner, D. Koeberle, R. Von-moos, P. Saletti, D. Rauch et al., Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: A randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK, Ann Oncol, vol.19, pp.1288-92, 2008.

K. M. Galal, M. Abdelsalam, E. E. Fawzy, S. Mansour, K. Zaghloul et al., Role of Bevacizumab as PostProgression Maintenance Therapy in Metastatic Colon Cancer, J Med Sci, vol.8, pp.452-60, 2008.

J. R. Hecht, E. Mitchell, T. Chidiac, C. Scroggin, C. Hagenstad et al., A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer, J Clin Oncol, vol.27, pp.672-80, 2009.

H. S. Hochster, L. L. Hart, R. K. Ramanathan, B. H. Childs, J. D. Hainsworth et al., Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: Results of the TREE study, J Clin Oncol, vol.26, pp.3523-3532, 2008.

A. F. Sobrero, J. Maurel, L. Fehrenbacher, W. Scheithauer, Y. A. Abubakr et al., EPIC: Phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer, J Clin Oncol, vol.26, pp.2311-2320, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00484211

N. Howlader, A. Noone, M. Krapcho, D. Miller, K. Bishop et al., SEER data submission, posted to the SEER web site, Cancer Statistics Review, 1975.

D. Rio, M. Mollevi, C. Vezzio-vie, and N. , Specific extracellular matrix remodeling signature of colon hepatic metastases, PLoS One, vol.8, p.74599, 2013.

E. Van-cutsem, A. Cervantes, and R. Adam, ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, Ann Oncol, vol.27, pp.1386-422, 2016.

D. Papamichael, R. Audisio, and B. Glimelius, Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013, Ann Oncol, vol.26, pp.463-76, 2015.

L. Talarico, G. Chen, and R. Pazdur, Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration, J Clin Oncol, vol.22, pp.4626-4657, 2004.

T. Aparicio, F. Pamoukdjian, and L. Quero, Colorectal cancer care in elderly patients: Unsolved issues, Dig Liver Dis, vol.48, pp.1112-1120, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01407526

A. Gouverneur, F. Salvo, and D. Berdaï, Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: A systematic review, J Geriatr Oncol, 2017.

M. Kozloff, J. Berlin, and P. Flynn, Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study, Oncology, vol.78, pp.329-368, 2010.

M. Rouyer, A. Fourrier-réglat, and D. Smith, Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: Results of the ETNA observational cohort, J Geriatr Oncol, vol.7, pp.187-94, 2016.

C. Jehn, L. Böning, and H. Kröning, Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer, Br J Cancer, vol.106, pp.274-282, 2012.

A. Fourrier-réglat, D. Smith, and M. Rouyer, Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort, Target Oncol, vol.9, pp.311-320, 2014.

E. Tahover, A. Hubert, and M. Temper, An observational cohort study of bevacizumab and chemotherapy in metastatic colorectal cancer patients: safety and efficacy with analysis by age group, Target Oncol, vol.10, pp.55-63, 2015.

M. Lindquist, VigiBase, the WHO Global ICSR Database System: Basic Facts, Drug Inf J, vol.42, pp.409-428, 2008.

I. R. Edwards and J. K. Aronson, Adverse drug reactions: definitions, diagnosis, and management, Lancet, vol.356, pp.1255-1264, 2000.

S. J. Evans, P. C. Waller, and S. Davis, Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports, Pharmacoepidemiol Drug Saf, vol.10, pp.483-489, 2001.

H. Hurwitz, L. Fehrenbacher, and W. Novotny, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N Engl J Med, vol.350, pp.2335-2377, 2004.

E. Van-cutsem, H. Lenz, and C. Köhne, Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer, J Clin Oncol, vol.33, pp.692-700, 2015.

J. Kwakman and C. Punt, Oral drugs in the treatment of metastatic colorectal cancer, Expert Opin Pharmacother, vol.17, pp.1351-61, 2016.

O. Bouché, G. D. Beretta, and P. G. Alfonso, The role of antiepidermal growth factor receptor monoclonal antibody monotherapy in the treatment of metastatic colorectal cancer, Cancer Treat Rev, vol.36, issue.1, pp.1-10, 2010.

H. Hurwitz, N. Tebbutt, and F. Kabbinavar, Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials, Oncologist, vol.18, pp.1004-1016, 2013.

E. Van-cutsem, C. Köhne, and E. Hitre, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer, N Engl J Med, vol.360, pp.1408-1425, 2009.

T. Asmis, E. Powell, and C. Karapetis, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)-results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care, Ann Oncol, vol.22, pp.118-144, 2011.

N. A. Jackson, J. Barrueco, and R. Soufi-mahjoubi, Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: Findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study, Cancer, vol.115, pp.2617-2646, 2009.

T. J. Price, D. Zannino, and K. Wilson, Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: A subgroup analysis from the AGITG MAX trial: An international randomised controlled trial of capecitabine, bevacizumab and mitomycin C, Ann Oncol, vol.23, pp.1531-1537, 2012.

G. Curigliano, E. L. Mayer, and H. J. Burstein, Cardiac Toxicity From Systemic Cancer Therapy: A Comprehensive Review, Prog Cardiovasc Dis, vol.53, pp.94-104, 2010.

G. Des-guetz, B. Uzzan, and K. Chouahnia, Cardiovascular toxicity of anti-angiogenic drugs, Target Oncol, vol.6, pp.197-202, 2011.

D. L. Hershman, J. D. Wright, and E. Lim, Contraindicated use of bevacizumab and toxicity in elderly patients with cancer, J Clin Oncol, vol.31, pp.3592-3601, 2013.

M. F. Sorrentino, J. Kim, and A. E. Foderaro, 5-fluorouracil induced cardiotoxicity: review of the literature, Cardiol J, vol.19, pp.453-461, 2012.

H. Tsai, J. Marshall, and S. Weiss, Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study, Ann Oncol, vol.24, pp.1574-1583, 2013.

H. I. Hurwitz, L. B. Saltz, and E. Van-cutsem, Venous thromboembolic events with chemotherapy plus bevacizumab: A pooled analysis of patients in randomized phase II and III studies, J Clin Oncol, vol.29, pp.1757-64, 2011.

D. Cunningham, I. Lang, and E. Marcuello, Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial, Lancet Oncol, vol.14, pp.1077-85, 2013.

D. J. Jonker, C. J. O'callaghan, and C. S. Karapetis, Cetuximab for the treatment of colorectal cancer, N Engl J Med, vol.357, pp.2040-2048, 2007.

T. Kogawa, A. Doi, and M. Shimokawa, Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer, Target Oncol, vol.10, pp.125-158, 2015.

A. Scope, A. Agero, and S. W. Dusza, Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption, J Clin Oncol, vol.25, pp.5390-5396, 2007.

Y. M. Alatawi and R. A. Hansen, Empirical estimation of under-reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), Expert Opin Drug Saf, vol.16, pp.761-768, 2017.

F. González-rubio, A. Calderón-larrañaga, and B. Poblador-plou, Underreporting of recognized adverse drug reactions by primary care physicians: an exploratory study, Pharmacoepidemiol Drug Saf, vol.20, pp.1287-94, 2011.

R. L. Siegel, K. D. Miller, and S. A. Fedewa, Colorectal cancer statistics, vol.67, pp.177-193, 2017.

N. Howlader, A. Noone, and M. Krapcho, SEER data submission, posted to the SEER web site, Cancer Statistics Review, 1975.

D. Rio, M. Mollevi, C. Vezzio-vie, and N. , Specific extracellular matrix remodeling signature of colon hepatic metastases, PloS One, vol.8, p.74599, 2013.

E. Van-cutsem, A. Cervantes, and R. Adam, ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, Ann Oncol, vol.27, pp.1386-1422, 2016.

D. Papamichael, R. Audisio, and B. Glimelius, International Society of Geriatric Oncology (SIOG) consensus recommendations

, Ann Oncol, vol.26, pp.463-476, 2015.

A. Gouverneur, F. Salvo, and D. Berdaï, Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: A systematic review, J Geriatr Oncol, 2017.

P. Soubeyran, C. Bellera, and J. Goyard, Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study, PloS One, vol.9, p.115060, 2014.

C. Handforth, A. Clegg, and C. Young, The prevalence and outcomes of frailty in older cancer patients: a systematic review, Ann Oncol, vol.26, pp.1091-1101, 2015.

C. A. Bellera, M. Rainfray, and S. Mathoulin-pélissier, Screening older cancer patients: first evaluation of the G-8 geriatric screening tool, Ann Oncol, vol.23, pp.2166-2172, 2012.

D. Saliba, M. Elliott, and L. Z. Rubenstein, The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community, J Am Geriatr Soc, vol.49, pp.1691-1699, 2001.

M. P. Lawton and E. M. Brody, Assessment of older people: self-maintaining and instrumental activities of daily living, The Gerontologist, vol.9, pp.179-186, 1969.

S. Katz, A. B. Ford, and R. W. Moskowitz, Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function, J Geriatr Oncol, vol.185, pp.8-15, 1963.

L. Biganzoli, L. Boni, and D. Becheri, Evaluation of the cardiovascular health study (CHS) instrument and the Vulnerable Elders Survey-13 (VES-13) in elderly cancer patients. Are we still missing the right screening tool?, Target Oncol, vol.24, pp.311-319, 2013.

D. Smith, A. Sa-cunha, and M. Rouyer, Outcomes according to tumor RAS and BRAF mutation status in patients treated with cetuximab in 1st-line treatment of unresectable metastatic colorectal cancer (mCRC): Updated results from EREBUS cohort, Ann Oncol, vol.28, issue.suppl_3, p.327, 2017.

, Effectivité et sécurité d'emploi des thérapies ciblées chez les sujets âgés et/ou fragiles en comparaison aux sujets jeunes et/ou non fragiles 108 17. National Cancer Institute Cancer Therapy Evaluation Program (CTEP). Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0, DCTD, 2006.

P. Therasse, S. G. Arbuck, and E. A. Eisenhauer, New Guidelines to Evaluate the Response to Treatment in Solid Tumors, J Natl Cancer Inst, vol.92, pp.205-216, 2000.

D. B. Rubin, Multiple Imputation after 18+ Years, J. Am. Stat. Assoc, 1996.

T. Aparicio, F. Pamoukdjian, and L. Quero, Colorectal cancer care in elderly patients: Unsolved issues. Dig Liver Dis, vol.48, pp.1112-1118, 2016.

C. Köhne, D. Cunningham, D. Costanzo, and F. , Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients, Ann Oncol, vol.13, pp.308-317, 2002.

F. Kabbinavar, C. Irl, A. Zurlo, and H. Hurwitz, Bevacizumab improves the overall and progression-free survival of patients with metastatic colorectal cancer treated with 5-fluorouracil-based regimens irrespective of baseline risk, Oncology, vol.75, pp.215-223, 2008.

E. Desot, L. De-mestier, and J. Volet, Prognostic factors in patients with non resectable metastatic colorectal cancer in the era of targeted biotherapies: relevance of Köhne's risk classification, Dig Liver Dis, vol.45, pp.330-335, 2013.

L. Repetto, L. Fratino, and R. A. Audisio, Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study, J Clin Oncol, vol.20, pp.494-502, 2002.

M. Kozloff, J. Berlin, and P. Flynn, Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study, Oncology, vol.78, pp.329-339, 2010.

S. Parakh, H. Wong, and R. Rai, Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia, J Geriatr Oncol, vol.6, pp.387-394, 2015.

, Effectivité et sécurité d'emploi des thérapies ciblées chez les sujets âgés et/ou

D. Papamichael, R. Audisio, and B. Glimelius, Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations, 2013.

, Ann. Oncol, vol.26, pp.463-476, 2015.

J. Phelip, O. Bouch-e, and T. Conroy, Cancer colorectal m etastatique. Th esaurus National de Canc erologie Digestive, 2014.

F. Sclafani and D. Cunningham, Bevacizumab in elderly patients with metastatic colorectal cancer, J. Geriatr. Oncol, vol.5, pp.78-88, 2014.

L. Talarico, G. Chen, and R. Pazdur, Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration, J. Clin. Oncol, pp.22-4626, 2004.

, Plan cancer, 2003.

T. Aparicio, S. Lavau-denes, and J. M. Phelip, Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02), Ann. Oncol, pp.27-121, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01910082

M. T. Seymour, L. C. Thompson, and H. S. Wasan, Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial, Lancet, vol.377, pp.1749-1759, 2011.

D. Cunningham, I. Lang, and E. Marcuello, Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial, Lancet Oncol, pp.14-1077, 2013.

F. F. Kabbinavar, J. Schulz, and M. Mccleod, Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial, J. Clin. Oncol, pp.23-3697, 2005.

S. Parakh, H. Wong, and R. Rai, Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia, J. Geriatr. Oncol, vol.6, pp.387-394, 2015.

V. Quipourt, V. Jooste, and V. Cottet, Comorbidities alone do not explain the undertreatment of colorectal cancer in older adults: a French population-based study, J. Am. Geriatr. Soc, pp.59-694, 2011.

P. Ward, J. R. Hecht, and H. Wang, Physical function and quality of life in frail and/or elderly patients with metastatic colorectal cancer treated with capecitabine and bevacizumab: an exploratory analysis, J. Geriatr. Oncol, vol.5, pp.368-375, 2014.

P. Soubeyran, From suboptimal to optimal treatment in older patients with cancer, J. Geriatr. Oncol, vol.4, pp.291-293, 2013.

P. Caillet, F. Canoui-poitrine, and J. Vouriot, Comprehensive geriatric assessment in the decision-making process in elderly patients with cancer: ELCAPA study, J. Clin. Oncol, vol.29, pp.3636-3642, 2011.

P. Soubeyran, C. Bellera, and J. Goyard, Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study, PLoS One, vol.9, p.115060, 2014.

A. Fourrier-r-eglat, D. Smith, and M. Rouyer, Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort, Target Oncol, vol.9, pp.311-319, 2014.

D. Smith, E. Terrebonne, and M. Rouyer, Chemotherapy and targeted agents for colorectal cancer in a real-life setting anticipate guidelines: the COLCHIC cohort study, Fundam. Clin. Pharmacol, pp.27-113, 2013.

, La concordance entre les sources a été évaluée en utilisant le pourcentage de concordance pour le CCRm et le coefficient kappa (k) pour les comorbidités. Résultats. -La concordance pour le CCR primitif et pour le CCRm était plus élevée en utilisant tous les types de codes de diagnostic qu'uniquement le code principal (respectivement 95 % vs 53 % pour le CCR primitif et 91 % vs 24 % pour le CCRm). La concordance était substantielle (k 0,65) pour les maladies cardiovasculaires, notamment la fibrillation auriculaire (k 0,77) et l'hypertension (k 0,68), ª 2016 Soci et e Franc ßaise de Pharmacologie et de Th erapeutique Fundamental & Clinical Pharmacology diagnostic (principal, rélié et associés) enregistrés dans le PMSI pour les séjours de ces patients ont été extraits

, Ces résultats sont rassurants en ce qui concerne la détection des CCRm dans le PMSI, lorsque tous les types de codes de diagnostic sont considérés et utiles pour mieux choisir les comorbidités potentiellement identifiables via le PMSI chez des patients âgés atteints de CCRm, 2017.

, Mots clés : Concordance ; Codes de la classification internationale des maladies (CIM-10) ; Dossiers médicaux ; Cancer colorectal

, Comorbidités References

. Globocan, , 2012.

F. Binder-foucard, N. Bossard, P. Delafosse, A. Belot, A. Woronoff et al., Cancer incidence and mortality in France over the 1980-2012 period: solid tumors, Rev Epidemiol Sante Publique, vol.62, pp.95-108, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01915012

D. Rio, M. Mollevi, C. Vezzio-vie, N. Bibeau, F. Ychou et al., Specific extracellular matrix remodeling signature of colon hepatic metastases, PloS One, vol.8, p.74599, 2013.

K. Martin-latry and B. Bégaud, Pharmacoepidemiological research using French reimbursement databases: yes we can!, Pharmacoepidemiol Drug Saf, vol.19, pp.256-65, 2010.

C. Quantin, L. Goaster, C. Allaert, F. A. Toussaint, and E. , Rev Epidemiol Sante Publique, vol.64, pp.3-4, 2016.

P. Blotière, J. Rudant, A. Barré, A. Racine, A. Weill et al., Conditions of prescription of anti-TNF agents in newly treated patients with inflammatory bowel disease in France, Dig Liver Dis, vol.48, pp.620-625, 2011.

A. Neumann, G. Maura, A. Weill, P. Ricordeau, A. F. Allemand et al., Comparative effectiveness of rosuvastatin versus simvastatin in primary prevention among new users: a cohort study in the French national health insurance database, Pharmacoepidemiol Drug Saf, vol.23, pp.240-50, 2014.

A. Weill, M. Païta, P. Tuppin, J. Fagot, A. Neumann et al., Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus, Pharmacoepidemiol Drug Saf, vol.19, pp.1256-62, 2010.

J. Bezin, P. Girodet, S. Rambelomanana, M. Touya, P. Ferreira et al., Choice of ICD-10 codes for the identification of acute coronary syndrome in the French hospitalization database, Fundam Clin Pharmacol, vol.29, pp.586-91, 2015.

L. Sahli, M. Lapeyre-mestre, H. Derumeaux, and G. Moulis, Positive predictive values of selected hospital discharge diagnoses to identify infections responsible for hospitalization in the French national hospital database, Pharmacoepidemiol Drug Saf, vol.25, pp.785-794, 2016.

A. Gouverneur, M. Rouyer, A. Grelaud, P. Robinson, F. Colombani et al., How are elderly patients treated after a diagnosis of metastatic colorectal cancer in real-life practice? A study in a French teaching hospital, Fundam Clin Pharmacol, vol.31, pp.104-113, 2016.

J. R. Landis and G. G. Koch, The measurement of observer agreement for categorical data, Biometrics, vol.33, pp.159-74, 1977.

. Inca, Algorithme de sélection des hospitalisations liées à la prise en charge du cancer dans les bases nationales d'activité hospitalière de court séjour « algorithme cancer, vol.27, 2016.

, Fiche pathologie : Cancer du côlon actif, 2016.

C. Quantin, E. Benzenine, M. Hägi, B. Auverlot, M. Abrahamowicz et al., Evaluation of medical information systems as a mean of identification of incident cases of colorectal cancer

, Sante Publique Vandoeuvre-lès-Nancy Fr, vol.26, pp.55-63, 2014.

S. Doat, S. Samson, A. Fagot-campagna, P. Tuppin, and F. Menegaux, Estimation of breast, prostate, and colorectal cancer incidence using a French administrative database (general sample of health insurance beneficiaries)

, Rev Epidemiol Sante Publique, vol.64, pp.145-52, 2016.

A. Bannay, C. Chaignot, P. Blotière, M. Basson, A. Weill et al., The best use of the Charlson Comorbidity Index with electronic health care database to predict mortality, Med Care, vol.54, pp.188-94, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01817541

R. L. Siegel, K. D. Miller, and S. A. Fedewa, Colorectal cancer statistics, CA Cancer J Clin, vol.67, pp.177-193, 2017.

N. Howlader, A. Noone, and M. Krapcho, SEER data submission, posted to the SEER web site, Cancer Statistics Review, 1975.

D. Rio, M. Mollevi, C. Vezzio-vie, and N. , Specific extracellular matrix remodeling signature of colon hepatic metastases, PloS One, vol.8, p.74599, 2013.

M. G. Fakih, Metastatic colorectal cancer: current state and future directions, J Clin Oncol, vol.33, pp.1809-1824, 2015.

E. Van-cutsem, A. Cervantes, and R. Adam, ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, Ann Oncol, vol.27, pp.1386-1422, 2016.

D. Papamichael, R. Audisio, and B. Glimelius, Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013, Ann Oncol, vol.26, pp.463-476, 2015.

A. Gouverneur, F. Salvo, and D. Berdaï, Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: A systematic review, J Geriatr Oncol, 2017.

C. Jehn, L. Böning, and H. Kröning, Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer, Br J Cancer, vol.106, pp.274-278, 2012.

M. Rouyer, A. Fourrier-réglat, and D. Smith, Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: Results of the ETNA observational cohort, J Geriatr Oncol, vol.7, pp.187-194, 2016.

N. J. Mccleary, J. Hubbard, and M. R. Mahoney, Challenges of conducting a prospective clinical trial for older patients: Lessons learned from NCCTG N0949 (alliance), J Geriatr Oncol, 2017.

S. Parakh, H. Wong, and R. Rai, Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia, J J Geriatr Oncol, vol.6, pp.387-394, 2015.

J. Bezin, M. Duong, and R. Lassalle, The national healthcare system claims databases in France, SNIIRAM and EGB: Powerful tools for pharmacoepidemiology, Pharmacoepidemiol Drug Saf, vol.26, pp.954-962, 2017.

C. Quantin, E. Benzenine, and M. Hägi, Evaluation of medical information systems as a mean of identification of incident cases of colorectal cancer

, Santé Publique, vol.26, pp.55-63, 2014.

A. Gouverneur, D. Dolatkhani, and M. Rouyer, Agreement between hospital discharge diagnosis codes and medical records to identify metastatic colorectal cancer and associated comorbidities in elderly patients, Rev Epidemiol Sante Publique, vol.65, pp.321-325, 2017.

T. Aparicio, S. Lavau-denes, and J. M. Phelip, Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02), Ann Oncol, vol.27, pp.121-127, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01910082

A. Gouverneur, P. Claraz, and M. Rousset, Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between Elderly and Younger Patients: a Study Using the International Pharmacovigilance Database, Target Oncol, 2017.

T. J. Price, D. Zannino, and K. Wilson, Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: A subgroup analysis from the AGITG MAX trial: Chapitre 4. Description, effectivité et sécurité d'emploi des différentes modalités de traitement chez les sujets âgés 153

, An international randomised controlled trial of capecitabine, bevacizumab and mitomycin C, Ann Oncol, vol.23, pp.1531-1536, 2012.

T. Aparicio, D. Gargot, and L. Teillet, Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients, Eur J Cancer, vol.74, pp.98-108, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01507477

C. A. Bellera, M. Rainfray, and S. Mathoulin-pélissier, Screening older cancer patients: first evaluation of the G-8 geriatric screening tool, Ann Oncol, vol.23, pp.2166-2172, 2012.

S. M. Lichtman, Clinical trial design in older adults with cancer-The need for new paradigms, J Geriatr Oncol, vol.3, pp.368-375, 2012.

V. Shankaran, D. Mummy, and L. Koepl, Survival and lifetime costs associated with first-line bevacizumab use in older patients with metastatic colorectal cancer, The Oncologist, vol.19, pp.892-899, 2014.

D. Cunningham, I. Lang, and E. Marcuello, Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an openlabel, randomised phase 3 trial, Lancet Oncol, vol.14, pp.1077-1085, 2013.

C. Bokemeyer, I. Bondarenko, and J. T. Hartmann, Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: The OPUS study, Ann Oncol, vol.22, pp.1535-1546, 2011.

J. Y. Douillard, S. Siena, and J. Cassidy, Final results from PRIME: Randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer, Ann Oncol, vol.25, pp.1346-1355, 2014.

T. S. Maughan, R. A. Adams, and C. G. Smith, Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: Results of the randomised phase 3 MRC COIN trial, The Lancet, vol.377, pp.2103-2114, 2011.

, Chapitre 4. Description, effectivité et sécurité d'emploi des différentes modalités de traitement

A. Chiang and J. Massagué, Molecular basis of metastasis, N. Engl. J. Med, vol.359, issue.26, pp.2814-2837, 2008.

K. Naxerova, J. G. Reiter, and E. Brachtel, Origins of lymphatic and distant metastases in human colorectal cancer, Science, vol.357, issue.6346, pp.55-60, 2017.

, Tumeur maligne, affection maligne du tissu lymphatique ou hématopoïétique, Cancer colorectal Adénocarcinome

F. Bray, A. Jemal, and N. Grey, Global cancer transitions according to the Human Development Index (2008-2030): a population-based study, Lancet Oncol, 2012.

A. Aouba, M. Eb, and G. Rey, Données sur la mortalité en France : principales causes de décès en 2008 et évolutions depuis, Bull. Epidémiologique Hebd, vol.22, pp.249-255, 2000.

R. L. Siegel, K. D. Miller, and S. A. Fedewa, Colorectal cancer statistics, vol.67, issue.3, pp.177-193, 2017.

N. Howlader, A. Noone, and M. Krapcho, National Cancer Institute. Bethesda, MD. Based on November 2016 SEER data submission, posted to the SEER web site, Cancer Statistics Review, 1975.

, Collection Les Données, 2016.

D. Rio, M. Mollevi, C. Vezzio-vie, and N. , Specific extracellular matrix remodeling signature of colon hepatic metastases, PloS One, vol.8, issue.9, p.74599, 2013.

E. Mitry, F. Rollot, and V. Jooste, Improvement in survival of metastatic colorectal cancer: are the benefits of clinical trials reproduced in population-based studies?, Eur. J. Cancer, vol.49, issue.13, pp.2919-2944, 2013.

S. Doat, A. Thiébaut, and S. Samson, Elderly patients with colorectal cancer: treatment modalities and survival in France. National data from the ThInDiT cohort study, Eur. J. Cancer, vol.50, issue.7, pp.1276-83, 2014.

E. Van-cutsem, A. Cervantes, and R. Adam, ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, Ann. Oncol, vol.27, issue.8, pp.1386-1422, 2016.

B. Gustavsson, G. Carlsson, and D. Machover, A review of the evolution of systemic chemotherapy in the management of colorectal cancer, Clin. Colorectal Cancer, vol.14, issue.1, pp.1-10, 2015.

M. Talbert, G. Willoquet, and R. Gervais, Guide Pharmaco Clinique 2011, le Moniteur des pharmacies, 2011.

, Agence nationale de sécurité du médicament et des produits de santé. 5-fluorouracil : RCP

D. Superfin, A. Iannucci, and A. Davies, Commentary: Oncologic drugs in patients with organ dysfunction: a summary, The Oncologist, vol.12, issue.9, pp.1070-83, 2007.

, Annexes 168

, European Medicines Agency. Xeloda : EPAR -Product Information

, Agence nationale de sécurité du médicament et des produits de santé, 2016.

, Agence nationale de sécurité du médicament et des produits de santé. Campto : RCP -(dernière mise à jour

, INCa Situation de la chimiothérapie des cancers -rapport 2013. Collection état des lieux & des connaissances, ouvrage collectif édité par l'INCa, 2014.

, European Medicines Agency. Avastin : EPAR -Product Information

, European Medicines Agency. Zaltrap : EPAR -Product Information

, European Medicines Agency. Cyramza : EPAR -Product Information

, European Medicines Agency. Erbitux : EPAR -Product Information

A. Lièvre, J. Bachet, L. Corre, and D. , KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer, Cancer Res, vol.66, issue.8, pp.3992-3997, 2006.

, European Medicines Agency. Vectibix : EPAR -Product Information

C. Bokemeyer, I. Bondarenko, and J. T. Hartmann, Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: The OPUS study, Ann. Oncol, vol.22, issue.7, pp.1535-1581, 2011.

E. Van-cutsem, C. Köhne, and E. Hitre, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer, N. Engl. J. Med, vol.360, issue.14, pp.1408-1425, 2009.

C. S. Karapetis, S. Khambata-ford, and D. J. Jonker, K-ras mutations and benefit from cetuximab in advanced colorectal cancer, N. Engl. J. Med, vol.359, issue.17, pp.1757-65, 2008.

R. G. Amado, M. Wolf, and M. Peeters, Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer, J. Clin. Oncol, vol.26, issue.10, pp.1626-1634, 2008.

J. Douillard, K. Oliner, and S. Siena, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer, N. Engl. J. Med, vol.369, issue.11, pp.1023-1057, 2013.

M. Sorich, M. Wiese, and A. Rowland, Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials, Ann. Oncol, vol.26, issue.1, pp.13-21, 2015.

, Annexes 169

N. Piton, E. Lonchamp, and F. Nowak, Real-Life Distribution of KRAS and NRAS Mutations in Metastatic Colorectal Carcinoma from French Routine Genotyping, Cancer Epidemiol. Biomarkers Prev, vol.24, issue.9, pp.1416-1424, 2015.

O. Bouché, G. D. Beretta, P. G. Alfonso, and M. Geissler, The role of anti-epidermal growth factor receptor monoclonal antibody monotherapy in the treatment of metastatic colorectal cancer, Cancer Treat. Rev, vol.36, issue.1, pp.1-10, 2010.

D. J. Jonker, C. J. O'callaghan, and C. S. Karapetis, Cetuximab for the treatment of colorectal cancer, N. Engl. J. Med, vol.357, issue.20, pp.2040-2048, 2007.

T. Kogawa, A. Doi, and M. Shimokawa, Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer, Target. Oncol, vol.10, issue.1, pp.125-133, 2015.

A. Scope, A. Agero, and S. W. Dusza, Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption, J. Clin. Oncol, vol.25, issue.34, pp.5390-5396, 2007.

, European Medicines Agency. Stivarga : EPAR -Product Information

, Le cancer colorectal : importance d'une prise en charge partagée

J. Phelip, O. Bouché, and T. Conroy, Cancer colorectal métastatique ». Thésaurus National de Cancérologie Digestive, 2016.

H. Hurwitz, L. Fehrenbacher, and W. Novotny, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N. Engl. J. Med, vol.350, issue.23, pp.2335-2377, 2004.

F. Kabbinavar, C. Irl, A. Zurlo, and H. Hurwitz, Bevacizumab improves the overall and progression-free survival of patients with metastatic colorectal cancer treated with 5-fluorouracil-based regimens irrespective of baseline risk, Oncology, vol.75, issue.3-4, pp.215-238, 2008.

L. B. Saltz, S. Clarke, and E. Díaz-rubio, Bevacizumab in combination with oxaliplatinbased chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study, J. Clin. Oncol, vol.26, issue.12, pp.2013-2022, 2008.

C. Cremolini, F. Loupakis, and C. Antoniotti, FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study, Lancet Oncol, vol.16, issue.13, pp.1306-1315, 2015.

D. Cunningham, I. Lang, and E. Marcuello, Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial, Lancet Oncol, 2013.

N. C. Tebbutt, K. Wilson, and V. J. Gebski, Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: Results of the Australasian Gastrointestinal Trials Group randomized phase III MAX study, J. Clin. Oncol, vol.28, pp.3191-3199, 2010.

E. Van-cutsem, C. Köhne, and I. Láng, Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: Updated analysis of Annexes 170 overall survival according to tumor KRAS and BRAF mutation status, J. Clin. Oncol, vol.29, issue.15, pp.2011-2020, 2011.

E. Van-cutsem, H. Lenz, and C. Köhne, Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer, J. Clin. Oncol, 2015.

T. S. Maughan, R. A. Adams, and C. G. Smith, Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: Results of the randomised phase 3 MRC COIN trial, The Lancet, 2011.

C. Bokemeyer, I. Bondarenko, and A. Makhson, Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer, J. Clin. Oncol, vol.27, issue.5, pp.663-71, 2009.

C. Bokemeyer, C. Köhne, and F. Ciardiello, FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer, Eur. J. Cancer, vol.51, issue.10, pp.1243-1252, 2015.

J. Y. Douillard, S. Siena, and J. Cassidy, Final results from PRIME: Randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer, Ann. Oncol, vol.25, issue.7, pp.1346-55, 2014.

K. M. Tveit, T. Guren, and B. Glimelius, Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study, J. Clin. Oncol, vol.30, issue.15, pp.1755-62, 2012.

. Qu'est-ce and . Qu,

, INCa Etat des lieux et perspectives en oncogériatrie. Collection rapports & synthèses, ouvrage collectif édité par l'INCa, 2009.

T. Aparicio, F. Pamoukdjian, and L. Quero, Colorectal cancer care in elderly patients: Unsolved issues. Dig. Liver Dis, vol.48, issue.10, pp.1112-1118, 2016.

, Recommandations de bonnes pratiques professionnelles -Évaluation et prise en charge des personnes âgées faisant des chutes répétées

S. Legrain, Consommation Médicamenteuse chez le Sujet Agé -Consommation, Prescription

J. Piccirillo, A. Vlahiotis, and L. Barrett, The changing prevalence of comorbidity across the age spectrum, Crit. Rev. Oncol. Hematol, vol.67, issue.2, pp.124-156, 2008.

S. K. Inouye, S. Studenski, M. E. Tinetti, and G. A. Kuchel, Geriatric Syndromes: Clinical, Research and Policy Implications of a Core Geriatric Concept, J. Am. Geriatr. Soc, vol.55, issue.5, pp.780-791, 2007.

E. Paillaud, E. Liuu, and M. Laurent, Geriatric syndromes increased the nutritional risk in elderly cancer patients independently from tumour site and metastatic status. The ELCAPA-05 cohort study, Clin. Nutr, vol.33, issue.2, pp.330-335, 2014.

, Annexes 171

K. Rockwood, X. Song, and A. Mitnitski, Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey, CMAJ Can. Med. Assoc. J. J. Assoc. Medicale Can, vol.183, issue.8, pp.487-494, 2011.

E. Liuu, P. Caillet, and H. Curé, Comprehensive geriatric assessment (CGA) in elderly with cancer: For whom?

, Rev. Med. Interne, vol.37, issue.7, pp.480-488, 2016.

L. Balducci and M. Extermann, Management of cancer in the older person: a practical approach, The Oncologist, vol.5, issue.3, pp.224-237, 2000.

C. A. Bellera, M. Rainfray, and S. Mathoulin-pélissier, Screening older cancer patients: first evaluation of the G-8 geriatric screening tool, Ann. Oncol, vol.23, issue.8, pp.2166-2172, 2012.

D. Saliba, M. Elliott, and L. Z. Rubenstein, The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community, J. Am. Geriatr. Soc, 2001.

L. Decoster, K. Van-puyvelde, and S. Mohile, Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations ?, Ann. Oncol. Off. J. Eur. Soc. Med. Oncol, vol.26, issue.2, pp.288-300, 2015.

C. Bellera and P. Soubeyran,

, Cancer Radiother, vol.19, issue.6-7, pp.382-385, 2015.

L. Z. Rubenstein, J. O. Harker, and A. Salvà, Screening for undernutrition in geriatric practice: developing the short-form mini-nutritional assessment (MNA-SF), J. Gerontol. A. Biol. Sci. Med. Sci, vol.56, issue.6, pp.366-372, 2001.

, International Society of Geriatric Oncology

, Société francophone d'onco-gériatrie (SoFOG)

, Plan cancer, 2003.

, Circulaire n°DHOS/SDO/2005/101 du 22 février 2005 relative à l'organisation des soins en cancérologie. Bulletin officiel du ministère chargé de la santé, pp.256-265, 2005.

S. Brio--bordeaux-recherche-intégrée-oncologie,

P. Pacan,

D. Papamichael, R. Audisio, and B. Glimelius, Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013, Ann. Oncol, vol.26, issue.3, pp.463-476, 2015.

M. T. Seymour, L. C. Thompson, and H. S. Wasan, Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial, Lancet, vol.377, issue.9779, pp.1749-1759, 2011.

, Annexes 172

T. Aparicio, S. Lavau-denes, and J. M. Phelip, Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02), Ann. Oncol, vol.27, issue.1, pp.121-127, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01910082

F. F. Kabbinavar, J. Schulz, and M. Mccleod, Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: Results of a randomized phase II trial, J. Clin. Oncol, vol.23, issue.16, pp.3697-705, 2005.

, Pharmacovigilance : assurer la sécurité d'emploi des médicaments -Perspectives politiques de l'OMS sur les médicaments, Pourquoi la pharmacovigilance est, 2004.

, Organisation de la pharmacovigilance nationale -ANSM : Agence nationale de sécurité du médicament et des produits de santé

M. Lindquist and . Vigibase, the WHO Global ICSR Database System: Basic Facts, vol.42, pp.409-419, 2008.

J. Montastruc, A. Sommet, H. Bagheri, and M. Lapeyre-mestre, Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database, Br. J. Clin. Pharmacol, vol.72, issue.6, pp.905-908, 2011.

B. Bégaud, Dictionnaire de pharmaco-épidémiologie, ARME-Pharmacovigilance Editions, 1998.

M. Elseviers, B. Wettermark, and A. B. Almarsdóttir, Drug Utilization Research: Methods and Applications. First Edition, 2016.

J. Bezin, M. Duong, and R. Lassalle, The national healthcare system claims databases in France, SNIIRAM and EGB: Powerful tools for pharmacoepidemiology, Pharmacoepidemiol. Drug Saf, vol.26, issue.8, pp.954-962, 2017.

S. Parakh, H. Wong, and R. Rai, Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia, J. Geriatr. Oncol, vol.6, issue.5, pp.387-394, 2015.

M. Kozloff, J. Berlin, and P. Flynn, Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study, Oncology, vol.78, issue.5-6, pp.329-339, 2010.

V. Shankaran, D. Mummy, and L. Koepl, Adverse events associated with bevacizumab and chemotherapy in older patients with metastatic colorectal cancer, Clin. Colorectal Cancer, vol.12, issue.3, pp.204-213, 2013.

H. Tsai, J. Marshall, and S. Weiss, Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study, Ann. Oncol, vol.24, issue.6, pp.1574-1583, 2013.

J. A. Meyerhardt, L. Li, and H. K. Sanoff, Effectiveness of bevacizumab with first-line combination chemotherapy for medicare patients with stage IV colorectal cancer, J. Clin. Oncol, vol.30, issue.6, pp.608-623, 2012.

C. Jehn, L. Böning, and H. Kröning, Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer, Br. J. Cancer, vol.106, issue.2, pp.274-282, 2012.

R. Hofheinz, V. Petersen, and M. Kindler, Bevacizumab in first-line treatment of elderly patients with metastatic colorectal cancer: German community-based observational cohort study results, BMC Cancer, vol.14, p.761, 2014.

A. Fu, H. Tsai, and J. Marshall, Utilization of bevacizumab in US elderly patients with colorectal cancer receiving chemotherapy, J. Oncol. Pharm. Pract, vol.20, issue.5, pp.332-372, 2014.

M. Rouyer, A. Fourrier-réglat, and D. Smith, Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: Results of the ETNA observational cohort, J. Geriatr. Oncol, vol.7, issue.3, pp.187-94, 2016.

, Harmonisation of technical requirements for registration of pharmaceuticals for human use, Studies in support of special populations: geriatrics E7, 1993.

A. Surbone, M. Kagawa-singer, C. Terret, and L. Baider, The illness trajectory of elderly cancer patients across cultures: SIOG position paper, Ann. Oncol, vol.18, issue.4, pp.633-638, 2007.

L. F. Hutchins, J. M. Unger, and J. J. Crowley, Underrepresentation of patients 65 years of age or older in cancer-treatment trials, N. Engl. J. Med, vol.341, issue.27, pp.2061-2067, 1999.

J. H. Lewis, M. L. Kilgore, and D. P. Goldman, Participation of patients 65 years of age or older in cancer clinical trials, J. Clin. Oncol, vol.21, issue.7, pp.1383-1389, 2003.

L. Talarico, G. Chen, and R. Pazdur, Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration, J. Clin. Oncol, vol.22, issue.22, pp.4626-4631, 2004.

C. Townsley, G. Pond, and B. Peloza, Analysis of treatment practices for elderly cancer patients in Ontario, Canada. J. Clin. Oncol, vol.23, issue.16, pp.3802-3812, 2005.

K. Yee, J. Pater, and L. Pho, Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier?, J. Clin. Oncol, vol.21, issue.8, pp.1618-1641, 2003.

R. Jennens, G. Giles, and R. Fox, Increasing underrepresentation of elderly patients with advanced colorectal or non-small-cell lung cancer in chemotherapy trials, Intern. Med. J, vol.36, issue.4, pp.216-236, 2006.

M. Oken, R. Creech, and D. Tormey, Toxicity and response criteria of the Eastern Cooperative Oncology Group, Am. J. Clin. Oncol, vol.5, issue.6, pp.649-55, 1982.

P. Ward, J. R. Hecht, and H. Wang, Physical function and quality of life in frail and/or elderly patients with metastatic colorectal cancer treated with capecitabine and bevacizumab: an exploratory analysis, J. Geriatr. Oncol, vol.5, issue.4, pp.368-375, 2014.

H. Sorbye, P. Pfeiffer, and N. Cavalli-björkman, Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients, Cancer, vol.115, pp.4679-4687, 1920.

L. A. Torre, F. Bray, and R. L. Siegel, Global cancer statistics, 2012. CA, Cancer J. Clin, vol.65, issue.2, pp.87-108, 2015.

T. Asmis, E. Powell, and C. Karapetis, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care, Ann. Oncol, vol.22, issue.1, pp.118-144, 2011.

N. A. Jackson, J. Barrueco, and R. Soufi-mahjoubi, Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: Findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study, Cancer, vol.115, issue.12, pp.2617-2646, 2009.

, Annexes 174

T. J. Price, D. Zannino, and K. Wilson, Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: A subgroup analysis from the AGITG MAX trial: An international randomised controlled trial of capecitabine, bevacizumab and mitomycin C, Ann. Oncol, vol.23, issue.6, pp.1531-1537, 2012.

G. Rosati, G. Aprile, G. G. Cardellino, and A. Avallone, A review and assessment of currently available data of the EGFR antibodies in elderly patients with metastatic colorectal cancer, J. Geriatr. Oncol, vol.7, issue.2, pp.134-141, 2016.

F. Sclafani and D. Cunningham, Bevacizumab in elderly patients with metastatic colorectal cancer, J. Geriatr. Oncol, vol.5, issue.1, pp.78-88, 2014.

N. J. Mccleary, J. Hubbard, and M. R. Mahoney, Challenges of conducting a prospective clinical trial for older patients: Lessons learned from NCCTG N0949 (alliance), J. Geriatr. Oncol, 2017.

A. F. Sobrero, J. Maurel, and L. Fehrenbacher, EPIC: Phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer, J. Clin. Oncol, vol.26, issue.14, pp.2311-2320, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00484211

S. B. Winther, T. L. Jørgensen, P. Pfeiffer, and C. Qvortrup, Can we predict toxicity and efficacy in older patients with cancer? Older patients with colorectal cancer as an example, ESMO Open, vol.1, issue.3, p.21, 2016.

S. M. Lichtman, Clinical trial design in older adults with cancer-The need for new paradigms, J. Geriatr. Oncol, vol.3, issue.4, pp.368-375, 2012.

B. Seruga, A. J. Templeton, and F. Badillo, Under-reporting of harm in clinical trials, Lancet Oncol, vol.17, issue.5, pp.209-219, 2016.

H. Hurwitz, T. Bekaii-saab, and J. Bendell, Safety and effectiveness of bevacizumab treatment for metastatic colorectal cancer: final results from the Avastin(®) RegistryInvestigation of Effectiveness and Safety (ARIES) observational cohort study, Clin. Oncol, vol.26, issue.6, pp.323-355, 2014.

P. Soubeyran, C. Bellera, and J. Goyard, Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study, PloS One, 2014.

C. Handforth, A. Clegg, and C. Young, The prevalence and outcomes of frailty in older cancer patients: a systematic review, Ann. Oncol, vol.26, issue.6, pp.1091-1101, 2015.

M. Huisingh-scheetz and J. Walston, How should older adults with cancer be evaluated for frailty?, J. Geriatr. Oncol, vol.8, issue.1, pp.8-15, 2017.

L. Biganzoli, S. Lichtman, and J. Michel, Oral single-agent chemotherapy in older patients with solid tumours: A position paper from the International Society of Geriatric Oncology (SIOG), Eur. J. Cancer, vol.51, issue.17, pp.2491-500, 2015.

S. J. Evans, P. C. Waller, and S. Davis, Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports, Pharmacoepidemiol. Drug Saf, vol.10, issue.6, pp.483-486, 2001.

E. Van-cutsem, J. Tabernero, and R. Lakomy, Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen, J. Clin. Oncol, vol.30, issue.28, pp.3499-506, 2012.

A. Grothey, E. Van-cutsem, and A. Sobrero, Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial, The Lancet, vol.381, issue.9863, pp.303-315, 2013.

, Annexes 175

Y. M. Alatawi and R. A. Hansen, Empirical estimation of under-reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), Expert Opin. Drug Saf, vol.16, issue.7, pp.761-767, 2017.

F. González-rubio, A. Calderón-larrañaga, and B. Poblador-plou, Underreporting of recognized adverse drug reactions by primary care physicians: an exploratory study, Pharmacoepidemiol. Drug Saf, vol.20, issue.12, pp.1287-1294, 2011.

M. Rouyer, A. Fourrier-réglat, and P. Noize, Efficacité et sécurité d'emploi du cétuximab en traitement de 1re ligne du cancer colorectal métastatique chez les sujets âgés : résultats de la cohorte, EREBUS. Rev. DÉpidémiologie Santé Publique, 2016.

A. Fourrier-réglat, D. Smith, and M. Rouyer, Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort, Target. Oncol, vol.9, issue.4, pp.311-319, 2014.

D. Smith, A. Sa-cunha, and M. Rouyer, Outcomes according to tumor RAS and BRAF mutation status in patients treated with cetuximab in 1st-line treatment of unresectable metastatic colorectal cancer (mCRC): Updated results from EREBUS cohort, Ann. Oncol, vol.28, issue.suppl_3, p.327, 2017.

S. Grille,

A. Hurria, K. Togawa, and S. Mohile, Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study, J. Clin. Oncol, vol.29, issue.25, pp.3457-65, 2011.

M. Extermann, I. Boler, and R. R. Reich, Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score, Cancer, vol.118, issue.13, pp.3377-3386, 2012.

M. E. Charlson, P. Pompei, K. L. Ales, and C. R. Mackenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation, J. Chronic Dis, vol.40, issue.5, pp.373-383, 1987.

, Stratégie de prise en charge en cas de dénutrition protéino-énergétique chez la personne âgée

C. Köhne, D. Cunningham, D. Costanzo, and F. , Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients, Ann. Oncol, vol.13, issue.2, pp.308-317, 2002.

C. Hocking, V. Broadbridge, and C. Karapetis, Equivalence of outcomes for rural and metropolitan patients with metastatic colorectal cancer in South Australia, Med. J. Aust, vol.201, issue.8, pp.462-468, 2014.

C. Quantin, E. Benzenine, and M. Hägi, Evaluation of medical information systems as a mean of identification of incident cases of colorectal cancer

, Santé Publique Vandoeuvre-Lès-Nancy Fr, vol.26, pp.55-63, 2014.

M. Prat, H. Derumeaux, and L. Sailler, Positive predictive values of peripheral arterial and venous thrombosis codes in French hospital database, Fundam. Clin. Pharmacol, 2017.

L. Sahli, M. Lapeyre-mestre, H. Derumeaux, and G. Moulis, Positive predictive values of selected hospital discharge diagnoses to identify infections responsible for hospitalization in the French national hospital database, Pharmacoepidemiol. Drug Saf, vol.25, issue.7, pp.785-789, 2016.

G. Moulis, J. Germain, and D. Adoue, Validation of immune thrombocytopenia diagnosis code in the French hospital electronic database, Eur. J. Intern. Med, vol.32, pp.21-22, 2016.

C. Davis, H. Naci, and E. Gurpinar, Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13, BMJ, vol.359, p.4530, 2017.

V. Shankaran, D. Mummy, and L. Koepl, Survival and lifetime costs associated with first-line bevacizumab use in older patients with metastatic colorectal cancer, The Oncologist, vol.19, issue.8, pp.892-899, 2014.

C. Schuurhuizen, A. Braamse, and I. Konings, Does severe toxicity affect global quality of life in patients with metastatic colorectal cancer during palliative systemic treatment? A systematic review, Ann. Oncol, vol.28, issue.3, pp.478-486, 2017.

A. Gouverneur, F. Salvo, D. Berdaï, N. Moore, A. Fourrier-réglat et al., Inclusion of elderly or frail patients in randomized controlled trials of targeted therapies for the treatment of metastatic colorectal cancer: a systematic review, J Geriatr Oncol, 2017.

,

A. Gouverneur, P. Claraz, M. Rousset, M. Arnaud, A. Fourrier-réglat et al., Comparative safety of targeted therapies for metastatic colorectal cancer between elderly and younger patients: a study using the international pharmacovigilance database, Target Oncol, 2017.

A. Gouverneur, J. Coutureau, J. Jové, M. Rouyer, A. Grelaud et al., Noize P; on behalf the ETNA study group and the EREBUS study group. Patterns of use, safety and effectiveness of targeted therapies in first-line treatment of metastatic colorectal cancer according to age and frailty: the STROMBOLI study, European Journal of Cancer

A. Gouverneur, M. Rouyer, A. Grelaud, P. Robinson, F. Colombani et al., How are elderly patients treated after a diagnosis of metastatic colorectal cancer in real-life practice? A study in a French teaching hospital, Fundam Clin Pharmacol, vol.31, pp.104-113, 2017.

A. Gouverneur, D. Dolatkhani, M. Rouyer, A. Grelaud-boussinot, F. Francis et al., Agreement between hospital diagnosis codes and medical records to identify metastatic colorectal cancer and comorbidities in elderly patients, Rev Epidemiol Sante Publique, vol.65, pp.321-326, 2017.

A. Gouverneur, J. Jové, A. Fourrier-réglat, J. Bezin, P. Noize et al., Inclusion of elderly patients in randomized controlled trials on targeted agents in the treatment of metastatic colorectal cancer: a systematic review, Treatment modalities and survival in elderly patients after a diagnosis of metastatic colorectal cancer in real-life practice: a French population based-study. En cours de relecture par les coauteurs Communications orales Gouverneur A, vol.40, pp.25-28, 2015.

A. Gouverneur, M. Rouyer, A. Grelaud, F. Colombani, E. Terrebonne et al., Évaluation de la prise en charge médicamenteuse des sujets âgés présentant un cancer colorectal métastatique : étude pilote observationnelle au CHU de Bordeaux, France. Revue d'Épidémiologie et de, S76. 9 ème Conférence Francophone d'Epidémiologie Clinique (EPICLIN), vol.63, pp.21-23, 2015.

A. Gouverneur, M. Arnaud, P. Claraz, A. Fourrier-réglat, A. Pariente et al., Safety of BRAF and MEK Inhibitors for Treatment of Metastatic melanoma: Analysis of the WHO Database of Adverse Event, Annexe 3. Autres publications et communications sur le thème du cancer, de la pharmacovigilance, des revues systématiques et méta-analyses Publications Rousset M, vol.40, p.85, 2017.

J. Faillie, P. Ferrer, A. Gouverneur, D. Driot, S. Berkemeyer et al., A new risk of bias checklist applicable to randomized trials, observational studies, and systematic reviews was developed and validated to be used for systematic reviews focusing on drug adverse events, J Clin Epidemiol, vol.86, pp.168-75, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01761705

P. Bosco-lévy, P. De-boissieu, A. Gouverneur, P. Noize, M. Molimard et al., National trends in use and costs of oral anticancer drugs in France: a populationbased study, Pharmacoepidemiol Drug Saf, pp.1-9, 2017.

H. Géniaux, D. Assaf, G. Miremont-salamé, B. Raspaud, A. Gouverneur et al., Performance of the Standardised MedDRA(®) Queries for Case Retrieval in the French Spontaneous Reporting Database, Communications orales Gouverneur A, vol.37, pp.19-21, 2014.

H. Géniaux, D. Assaf, G. Miremont-salamé, B. Raspaud, A. Gouverneur et al., Performance of the Standardised MedDRA Queries, 23. 18 ème Congrès annuel de la Société Française de Pharmacologie et de Thérapeutique (SFPT), vol.28, pp.22-24, 2014.

M. Rousset, A. Gouverneur, M. Arnaud, P. Claraz, A. Fourrier-réglat et al., Safety of BRAF and MEK Inhibitors for Treatment of Metastatic melanoma: Analysis of the WHO Database of Adverse Event, th International of Pharmacovigilance (ISOP), vol.40, pp.15-18, 2017.

J. Perino, A. Gouverneur, M. L. Laroche, M. C. Perault-pochat, M. Allouchery et al., Annexes, vol.181

G. Miremont-salamé, A. Pariente, A. Gouverneur, M. Arnaud, B. Berdaï et al., Efficacy of targeted therapies in metastatic colorectal cancer: meta-analysis, Serious drug adverse reactions: A retrospective and descriptive study from the French regions of Bordeaux, Limoges, and Poitiers, vol.40, pp.26-30, 2017.

J. Faillie, P. Ferrer, A. Gouverneur, D. Driot, S. Berkemeyer et al., Development and Validity of a Checklist Assessing the Risk of Bias of Randomized Trials, Observational Studies and Systematic Reviews Analyzing Drug Adverse Events, 48. 21 ème Congrès annuel de la Société Française de Pharmacologie et de Thérapeutique (SFPT), vol.31, pp.19-21, 2017.

J. Faillie, P. Ferrer, A. Gouverneur, D. Driot, S. Berkemeyer et al., Development and Validity of a Checklist Assessing the Risk of Bias of Randomized Trials, Observational Studies and Systematic Reviews Analyzing Drug Adverse Events, nd International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE), vol.25, pp.25-28, 2016.

M. Rouyer, A. Grelaud, P. Noize, C. Droz-perroteau, R. Lassalle et al., Oncopharmaco-épidémiologie : à propos de 10 ans d'expérience d'une plateforme de recherche bordelaise, 11 èmes Journées du Cancéropôle Grand Sud-Ouest (GSO), pp.5-6, 2015.

P. Noize, M. Rouyer, A. Grelaud, C. Droz, R. Lassalle et al., 10-year experience of a French research platform, st International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE), vol.24, pp.22-26, 2015.

M. Rouyer, A. Grelaud, P. Noize, C. Droz, R. Lassalle et al.,

, ème Colloque de pharmaco-épidémiologie PEP ADELF AFCROs, p.11

, Equipe Pharmaco-épidémiologie) -Inserm CIC1401 REFERENCE: Your Name(s) (for the acknowledgment section