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Poster display session

5177 - Epidermal growth factor receptor (EGFR) copy number (CN) as a biomarker of prognosis and panitumumab (Pan) benefit in RAS-wt advanced colorectal cancer (aCRC)

Date

09 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Translational Research;  Colon and Rectal Cancer

Presenters

Jenny Seligmann

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

J. Seligmann, H. Wood, S. Richman, F. Elliott, M. Taylor, E. Tinkler-Hundal, J. Barrett, M. Seymour, P. Quirke

Author affiliations

  • Leeds Institute Of Cancer And Pathology, University of Leeds, LS9 - Leeds/GB
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Resources

Abstract 5177

Background

Whilst RAS mutations predict which aCRC patients (pts) will not benefit from anti-EGFR agents, RAS-wt status does not reliably predict who will. Several studies report that high EGFR ligand expression (EREG/AREG) is predictive of anti-EGFR agent benefit but progression towards clinical utility is limited by lack of consensus on a clinical dichotomisation point and additional tumor material required. Here we explore EGFR copy number as a biomarker of prognosis and predictor of Pan benefit in a randomised trial in aCRC.

Methods

EGFR CN, EREG/AREG RNA expression, RAS/RAF mutations were assessed in tumor from 275 pts randomised to 2nd-line irinotecan (Ir) or IrPan (PICCOLO, Lancet Onc 14:749-59). EGFR CN status was measured by the Affymetrix OncoScan array, analysed using Biodiscovery Nexus software and defined as normal (2 copies) or gain (>2 copies). Prognostic analysis was in Ir alone pts. Predictive analysis, in the 234 RAS-wt pts, compared baseline values with outcomes using Cox proportional hazards models.

Results

196 (71.3%) pts were classified as EGFR gain and 79 (28.7%) as normal. EGFR gain was significantly associated with high EREG and AREG RNA expression (both p 

Conclusions

EGFR CN status may allow for further stratification for Pan benefit in RAS-wt patients. Normal EGFR CN status identified nearly 1/3 of pts without Pan benefit. This biomarker is consistent with EGFR ligand data, and is a DNA-based assay with a clearly definable dichotomised cut-point and therefore is of potential clinical utility.

Clinical trial identification

ISRCTN93248876

Legal entity responsible for the study

University of Leeds

Funding

Affymetrix

Disclosure

All authors have declared no conflicts of interest.

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