Abstract 3956
Background
Eph A2 promotes tumor growth, invasiveness and angiogenesis in mCRC. Targeting Eph A2 could overcome resistance to anti-epidermal growth factor receptor treatment in colon cancer preclinical models.
Methods
Formalin-fixed paraffin-embedded tumor specimens from 82 RAS wild type (WT) mCRC pts treated with cetuximab + FOLFIRI as first line therapy in the CAPRI GOIM trial were assessed for Eph A2 expression by immunohistochemistry. Eph A2 levels were evaluated developing an HSCORE [1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)] (range: 0-300). A cut off was set by ROC analysis to define high (>50) and low (≤50) Eph A2 levels.
Results
Eph A2 expression was found in 55/82 (67%) cases. According to HSCORE Eph A2 levels were low in 54 (66%) and high in 28 (34%) samples. Eph A2 expression resulted in mostly complete membranous staining. Tumor stroma was positive in 15/82 (18%) cases. In most of these cases an intense immune infiltrate was observed. Non-tumor adjacent normal mucosa was assessable in 34/82 samples. Eph A2 was expressed in 16/34 (47%), more frequently in dysplastic epithelial areas. A significant correlation between Eph A2 expression in tumor and stroma was found (p
Conclusions
Eph A2 levels were significantly associated with a worse PFS and an increase in PD in RAS WT mCRC pts treated with cetuximab + FOLFIRI as first line therapy in the CAPRI GOIM trial, in both right- and left-sided tumors. A similar trend was observed for OS. Eph A2 might represent an additional predictive biomarker of lack of efficacy in RAS WT mCRC pts treated with cetuximab + FOLFIRI.
Clinical trial identification
Legal entity responsible for the study
Department of Clinical and Experimental Medicine ‘F. Magrassi’ Università degli studi della Campania “Luigi Vanvitelli”, Naples, Italy.
Funding
AIRC
Disclosure
F. Ciardiello: Advisory boards: Merck Serono, Lilly, Roche, Bayer, Amgen, Pfizer. E. Martinelli: Advisory boards: Merck Serono, Amgen. All other authors have declared no conflicts of interest.