458O - Frequency of potentially actionable genetic alterations in EORTC SPECTAcolor

Abstract

The EORTC Screening Platform for Efficient Clinical Trial Access in advanced colorectal cancer (SPECTAcolor) is a prospective, Europe-wide screening program for molecular characterization of tumours to facilitate participation in clinical studies with targeted agents and enrolled more than 900 patients (pts). Here, we report on the first cohort screened with a large next generation sequencing (NGS) panel. 328 cancer genes were analysed in 389 colorectal cancer pts with NGS according to GCLP standards; limited gene fusions were assessed in a subset of samples. Genetic events were detected by an ISO 13485-accredited analysis pipeline. Driver events were annotated by curation of published literature. Out of the 389 pts, 370 pts were microsatellite stable (MSS) and 19 pts (4.8%) were highly microsatellite instable (MSI-H) by either immunohistochemistry or fragment length analysis. MSS and MSI-H tumors harboured a median of 3 (range 0- 16) and 8 potential “driver” mutations (range 3-16) respectively. Prevalence of mutations according to MSI status and tumor localization (left colon/rectum, L, or right colon, R) are listed in table 1. In addition to BRAF and MSI-H, we detected 1.6% of patients with BRCA2 mutation (L 0.8%, R 3.8%, MSI-H 5.3%), 1.9% with ERBB2 mutation (L 2.0%, R 1.0%), 2.5% with ERBB2 amplification, 3.5% with FGFR1/2/3 amplification, and in 16% of MSI-H patients TSC1 mutation as potentially actionable alterations. In addition, we observed single ALK and ROS fusions.Tabled 1Most frequent mutations according to location and MSI-H (%)MSS (n = 370)MSI-H (n = 19)totalleftrighttotalAPC77.880.873.621.1TP5372.276.562.352.6KRAS47.845.553.842.1PIK3CA17.614.125.547.4FBXW711.112.28.536.8BRAF10.55.1$22.636.8SOX98.16.213.221.1SMAD47.67.19.40ARD1A5.15.53.80NRAS5.14.37.50$ L vs R: p < 0.0001 Open table in a new tab $ L vs R: p < 0.0001 Gene panel sequencing identified new potential therapeutic targets in an approximated total of 10% of patients with colorectal cancer. The SPECTA programme provides an effective platform for identifying rare, potentially actionable genomic targets.