Author(s)

Jean-Philippe Metges^1,2, Erick Gamelin¹, Alain Volant², Olivier Capitain³, Jean-François Ramée⁴, Jean-Luc Raoul⁵, Jean-Yves Douillard^1,6, Pierre-Luc Etienne⁷, Isabelle Cumin⁸, Olivier Dupuis⁹, Roger Faroux¹⁰, Marie-Aude Coulon^11,23, Philippe Deguiral¹², Karine Bideau¹³, Nacr Eddine Achour¹⁴, Alain Gourlaouen¹⁵, Corinne Alleaume¹⁶, Annie Wdowik¹⁷, Laurent Miglianico^18,26, Yann Touchefeu¹⁹, Vincent Klein²⁰, Alain Penchet^21,24, Ludovic Rosenfeld²², Daniel Martin²³, Claire Stampfli²⁵, Jean-Jacques Auger²⁷, Alain Bargain²⁸, Murielle Broyer-Petit²⁹, Jérome Chettrit³⁰, Louis-Rémi De Ybarlucea¹¹, Serge Eloit³¹, Pierre Marie Girardot³², Nathalie Heresbach³³, Christian Laboisse¹⁹, Eric Lavoine³⁴, Gilles Lemasson³⁵, Claire Magois¹⁰, Sophie Michalak³⁶, Norbert Padilla³⁷, Joseph Politis³⁸, Frédéric Staroz³⁹, Bruno Turlin⁴⁰, Arnaud Uguen², Viorel Vasiliu³⁷, Véronique Verriele³, Fanny Marhuenda¹, Delphine Déniel Lagadec¹, Christian Riché¹, Françoise Grudé¹

¹Observatoire dédié au Cancer des régions Bretagne et Pays de la Loire, France.
²Centre Hospitalier Régional Universitaire (CHRU), Brest, France.
³Institut de Cancérologie de l’Ouest (ICO) Paul Papin, Angers, France.
⁴Centre Catherine de Sienne, Nantes, France.
⁵CRLCC Eugène Marquis, Rennes, France.
⁶ICO René Gauducheau, Nantes, France.
⁷Centre CARIO-HCPA, Plérin, France.
⁸Centre Hospitalier Bretagne Sud (CHBS), Lorient, France.
⁹Clinique Victor Hugo, Le Mans, France.
¹⁰Centre Hospitalier Départemental (CHD), La Roche-sur-Yon, France.
¹¹CH, Le Mans, France.
¹²Clinique Mutualiste de l’Estuaire, Saint-Nazaire, France.
¹³CHIC Quimper, France.
¹⁴Clinique Pasteur Lanroze, Brest, France.
¹⁵CH, MORLAIX, France.
¹⁶CH, Saint-Brieuc, France.
¹⁷CHBA Vannes, France.
¹⁸CHP, Saint-Grégoire, France.
¹⁹CHU, Nantes, France.
²⁰Hopital Privé Océane, Vannes, France.
²¹Clinique Saint-Michel et Sainte-Anne, Quimper, France.
²²Pole Santé Sarthe et Loire, La Flèche, France.
²³Polyclinique du Maine, Laval, France.
²⁴Polyclinique Sud Quimper, France.
²⁵CH Laval, France.
²⁶Polyclinique Cesson Sévigné, France.
²⁷Laboratoire d’anatomie et de cytologie pathologiques, Cholet, France.
²⁸Cabinet d’anatomie et de cytologie pathologiques, Saint-Malo, France.
²⁹Laboratoire d’anatomie et de cytologie pathologiques, Lorient, France.
³⁰Institut d’histopathologie, Nantes, France.
³¹Laboratoire de Pathologie Médicale, Laval, France.
³²ARMOR Pathologie, Plérin, France.
³³Laboratoire d’anatomie et de cytologie pathologiques, Rennes, France.
³⁴Laboratoire d’anatomie et de cytologie pathologiques, Angers, France.
³⁵Laboratoire Analyses Biologie Glasgow, Brest, France.
³⁶CHU Angers, France.
³⁷Centre d’anatomie et de cytologie pathologiques, Le Mans, France.
³⁸Cabinet d’anatomie et de cytologie pathologiques, Vannes, France.
³⁹Laboratoire d’anatomie et de cytologie pathologiques, Quimper, France.
⁴⁰CHU Rennes, France.

Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.

Metastatic Colorectal Cancer, Cetuximab, EGFR Expression

Metges, J. , Gamelin, E. , Volant, A. , Capitain, O. , Ramée, J. , Raoul, J. , Douillard, J. , Etienne, P. , Cumin, I. , Dupuis, O. , Faroux, R. , Coulon, M. , Deguiral, P. , Bideau, K. , Achour, N. , Gourlaouen, A. , Alleaume, C. , Wdowik, A. , Miglianico, L. , Touchefeu, Y. , Klein, V. , Penchet, A. , Rosenfeld, L. , Martin, D. , Stampfli, C. , Auger, J. , Bargain, A. , Broyer-Petit, M. , Chettrit, J. , De Ybarlucea, L. , Eloit, S. , Girardot, P. , Heresbach, N. , Laboisse, C. , Lavoine, E. , Lemasson, G. , Magois, C. , Michalak, S. , Padilla, N. , Politis, J. , Staroz, F. , Turlin, B. , Uguen, A. , Vasiliu, V. , Verriele, V. , Marhuenda, F. , Lagadec, D. , Riché, C. and Grudé, F. (2016) EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from “ERBITUX-OUEST”. Open Journal of Internal Medicine, 6, 56-67. doi: 10.4236/ojim.2016.62010.