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.
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.
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
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
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University of Leeds
All authors have declared no conflicts of interest.