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

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 o f 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.