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egfr expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from “ERBITUX-OUEST”

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Open Journal of Internal Medicine 2016年第2期6卷 56-67页

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 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 cytologie pathologiques Lorient France Institut d’histopathologie Nantes France Laboratoire de Pathologie Médicale Laval France ARMOR Pathologie Plérin France Laboratoire d’anatomie et de cytologie pathologiques Rennes France Laboratoire d’anatomie et de cytologie pathologiques Angers France Laboratoire Analyses Biologie Glasgow Brest France CHU Angers France Centre d’anatomie et de cytologie pathologiques Le Mans France Cabinet d’anatomie et de cytologie pathologiques Vannes France Laboratoire d’anatomie et de cytologie pathologiques Quimper France CHU 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.

关键词： Metastatic Colorectal Cancer Cetuximab egfr expression

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Spectrum of egfr aberrations and potential clinical implications:insights from integrative pan-cancer analysis

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Cancer Communications 2020年第1期40卷 43-59页

作者： Haijing Liu Bo Zhang Zhifu Sun Department of Pathology School of Basic Medical SciencesThird HospitalPeking University Health Science CenterBeijing100191P.R.China Division of Biomedical Statistics and Informatics Department of Health Sciences ResearchMayo ClinicRochesterMN55905USA

Background:Human epidermal growth factor receptor(egfr)is an oncogenic gene and one of top targets of precision therapy in lung cancer with egfr mutations.Although there are many reports for some individual cancers,comprehensive profiling of egfr mutations,overexpression,amplification,DNA methylation,and their clinical associations across many different cancers simultaneously was not available.This study aimed to fill the gap and provide insights to the alteration spectrum of egfr and its therapeutic and prognostic implications.Methods:The Cancer Genome Atlas(TCGA)datasets for 32 cancer types involving 11,314 patients were analyzed for alterations(mutations and amplification/deletion),abnormal expression and DNA methylation in egfr gene.Mutation frequency,genomic location distribution,functional impact,and clinical targeted therapy implication were compared among different cancer types,and their associations with patient survival were analyzed.Results:egfr alteration frequency,mutation sites across functional domains,amplification,overexpression,and DNA methylation patterns differed greatly among different cancer types.The overall mutation frequency in all cancers combined was relatively low.Targetable mutations,mainly in lung cancer,were primarily found in the Pkinase_Tyr domain.Glioblastoma multiforme had the highest rate of alterations,but it was dominated by gene amplification and most mutations were in the Furin-like domain where targeted therapy was less effective.Low-grade glioma often had gene amplification and increased egfr expression which was associated with poor outcome.Colon and pancreatic adenocarcinoma had very few egfr mutations;however,high egfr expression was significantly associated with short patient survival.Squamous cell carcinoma regardless of their sites(the head and neck,lung,or esophagus)exhibited similar characteristics with an alteration frequency of about 5.0%,was dominated by gene amplification,and had increased egfr expression generally associated with short patient survival.DNA me

关键词： egfr expression egfr mutation epidermal growth factor receptor pan-cancer profiling patient survival targeted therapy The Cancer Genome Atlas(TCGA)

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