TITLE:
EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from “ERBITUX-OUEST”
AUTHORS:
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
KEYWORDS:
Metastatic Colorectal Cancer, Cetuximab, EGFR Expression
JOURNAL NAME:
Open Journal of Internal Medicine,
Vol.6 No.2,
June
22,
2016
ABSTRACT: 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.