477P Genomically-matched therapy in refractory CRC according to ESCAT

Abstract

Next Generation Sequencing (NGS) emerges as an actionability-searching strategy in the molecularly heterogeneous context of colorectal cancer (CRC)1, but its clinical impact remains unknown in a refractory setting. We aim to determine the value of NGS in terms of enrolment in genomically-guided clinical trials (gCT) in a cohort of metastatic CRC (mCRC) patients (pts) according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT[E]) 2. 1Muzny et al, Nature 2012; 2Mateo et al, Ann Oncol 2018. Target population are pts with refractory mCRC included in NGS program (DNA seq for mutations [mut], amplifications [amp] or deletions [del] and RNA seq for fusions [fus]) for therapeutic purposes from 2015-2019. 159 pts have been identified, 122 left-sided (LC) vs 37 right-sided (RC). Basal molecular profile locally performed showed: 80 pts RAS WT (E IA), all treated with anti-EGFR; 9 pts BRAF V600E (E IA), 6/9 received BRAF-inhibitors; 3 pts MSI (E IB), 2/3 received immunotherapy. NGS (149 mut panel, 29 amp/del panel, 27 fus panel) was performed on archival FFPE samples of primary tumors (85%) and metastases (15%) of 113 LC and 36 RC. 10 pts have insufficient material. NGS unveiled druggable alterations different from basal profile in 24 pts (16%): 2 ERBB2 amp (EIB), 6 KRAS G12C mut (EIIIA), 3 ERBB2 mut (EIIIA), 5 PIK3CA mut in RAS –BRAF WT (EIVA), 3 BRAF nonV600E mut (EIVA), 4 RNF43 mut (EIVA), 1 MET amp (EIVA), distributed as 7 RC (19%) and 17 LC (15%). Only 4 pts were included in gCT, 5 deteriorated clinically and 15 were enrolled in other unmatched trials or received SoC because lack of slots in gCT. NGS unravels 16% of ESCAT-defined druggable alterations with final inclusion rate in gCT of 4/159 pts. Further data is needed to better define the value of NGS in mCRC, considering the evolving landscape of gCT and biomarkers, as well as basal tumor biology and clonal selection.