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Poster display session

3956 - Eph A2 expression is a predictive biomarker of poorer activity and efficacy of FOLFIRI + cetuximab in RAS WT metastatic colorectal cancer (mCRC) patients (pts) in the CAPRI GOIM trial

Date

11 Sep 2017

Session

Poster display session

Presenters

Claudia Cardone

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

C. Cardone1, M.C. Paul2, V. Moreno-Viedma2, G. Martini1, P.P. Vitiello1, D. Ciardiello1, V. Sforza1, T. Troiani1, S. Napolitano1, P. Vitale1, N. Zanaletti1, A.M. Rachiglio3, D. Rizzi4, E. Maiello5, N. Normanno6, M. Sibilia2, F. Ciardiello1, E. Martinelli1

Author affiliations

  • 1 Oncologia Medica, Dipartimento Di Internistica Clinica E Sperimentale “f. Magrassi”,, Università degli Studi della Campania Luigi Vanvitelli, 80121 - Napoli/IT
  • 2 Department Of Medicine I, Institute of Cancer Research, Vienna/AT
  • 3 Laboratory Of Pharmacogenomics, Centro Di Ricerche Oncologiche Di Mercogliano (crom), National Cancer Institute ‘Fondazione Giovanni Pascale', 80121 - Napoli/IT
  • 4 Trial Office, GOIM, Bari/IT
  • 5 Oncologia, IRCCS Casa Sollievo della Sofferenza, 71013 - San Giovanni Rotondo/IT
  • 6 Cell Biology Unit, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
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Resources

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.

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