摘要
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.
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.
作者
Jean-Philippe Metges
Erick Gamelin
Alain Volant
Olivier Capitain
Jean-François Ramée
Jean-Luc Raoul
Jean-Yves Douillard
Pierre-Luc Etienne
Isabelle Cumin
Olivier Dupuis
Roger Faroux
Marie-Aude Coulon
Philippe Deguiral
Karine Bideau
Nacr Eddine Achour
Alain Gourlaouen
Corinne Alleaume
Annie Wdowik
Laurent Miglianico
Yann Touchefeu
Vincent Klein
Alain Penchet
Ludovic Rosenfeld
Daniel Martin
Claire Stampfli
Jean-Jacques Auger
Alain Bargain
Murielle Broyer-Petit
Jérome Chettrit
Louis-Rémi De Ybarlucea
Serge Eloit
Pierre Marie Girardot
Nathalie Heresbach
Christian Laboisse
Eric Lavoine
Gilles Lemasson
Claire Magois
Sophie Michalak
Norbert Padilla
Joseph Politis
Frédéric Staroz
Bruno Turlin
Arnaud Uguen
Viorel Vasiliu
Véronique Verriele
Fanny Marhuenda
Delphine Déniel Lagadec
Christian Riché
Françoise Grudé
Jean-Philippe Metges;Erick Gamelin;Alain Volant;Olivier Capitain;Jean-François Ramée;Jean-Luc Raoul;Jean-Yves Douillard;Pierre-Luc Etienne;Isabelle Cumin;Olivier Dupuis;Roger Faroux;Marie-Aude Coulon;Philippe Deguiral;Karine Bideau;Nacr Eddine Achour;Alain Gourlaouen;Corinne Alleaume;Annie Wdowik;Laurent Miglianico;Yann Touchefeu;Vincent Klein;Alain Penchet;Ludovic Rosenfeld;Daniel Martin;Claire Stampfli;Jean-Jacques Auger;Alain Bargain;Murielle Broyer-Petit;Jérome Chettrit;Louis-Rémi De Ybarlucea;Serge Eloit;Pierre Marie Girardot;Nathalie Heresbach;Christian Laboisse;Eric Lavoine;Gilles Lemasson;Claire Magois;Sophie Michalak;Norbert Padilla;Joseph Politis;Frédéric Staroz;Bruno Turlin;Arnaud Uguen;Viorel Vasiliu;Véronique Verriele;Fanny Marhuenda;Delphine Déniel Lagadec;Christian Riché;Françoise Grudé(Observatoire dédié au Cancer des régions Bretagne et Pays de la Loire, France;Centre Hospitalier Régional Universitaire (CHRU), Brest, France;Institut de Cancérologie de l’Ouest (ICO) Paul Papin, Angers, France;Centre Catherine de Sienne, Nantes, France;CRLCC Eugène Marquis, Rennes, France;ICO René Gauducheau, Nantes, France;Centre CARIO-HCPA, Plérin, France;Centre Hospitalier Bretagne Sud (CHBS), Lorient, France;Clinique Victor Hugo, Le Mans, France;Centre Hospitalier Départemental (CHD), La Roche-sur-Yon, France;CH, Le Mans, France;Clinique Mutualiste de l’Estuaire, Saint-Nazaire, France;CHIC Quimper, France;Clinique Pasteur Lanroze, Brest, France;CH, MORLAIX, France;CH, Saint-Brieuc, France;CHBA Vannes, France;CHP, Saint-Grégoire, France;CHU, Nantes, France;Hopital Privé Océane, Vannes, France;Clinique Saint-Michel et Sainte-Anne, Quimper, France;Pole Santé Sarthe et Loire, La Flèche, France;Polyclinique du Maine, Laval, France;Polyclinique Sud Quimper, France;CH Laval, France;Polyclinique Cesson Sévigné, France;Laboratoire d’anatomie et de cytologie pathologiques, Cholet, France;Cabinet d’anatomie et de cytologie pathologiques, Saint-Malo, France;Laboratoire d’anatomie et de
