Genomically matched therapy in refractory colorectal cancer according to ESMO Scale for Clinical Actionability of Molecular Targets: experience of a comprehensive cancer center network.

Abstract

Efficiency of expanded genomic profiling (EGP) programmes in terms of final inclusion of patients in genomically matched therapies is still unknown. Fit patients with advanced and refractory colorectal cancer (CRC) were selected for an EGP programme. Next-generation sequencing (NGS) analysis from formalin-fixed paraffin-embedded tumour samples was performed. The purpose was to describe the prevalence of genomic alterations defined by the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), as well as the percentage of patients finally included in genomically guided clinical trials. In total, 187 patients were recruited. Mutational profile was obtained in 177 patients (10 patients were failure due to insufficient tumour sample), copy number alterations in 41 patients and fusions in 31 patients. ESCAT-defined alterations were detected in 28.8% of the intention-to-analyse population. BRAF V600E was clustered in ESCAT I, with a prevalence of 3.7%, KRAS G12C and ERBB2 amplification were clustered in ESCAT II, whose prevalence was 4.2% and 1.6%, respectively. Most alterations were classified in ESCAT III (mutations in ERBB2, PIK3CA or FGFR genes and MET amplification) and IV (mutations in BRAF non-V600E, ERBB3, FBXW7, NOTCH, RNF43), with a single prevalence under 5%, except for PIK3CA mutation (9%).The final rate of inclusion into genomically guided clinical trials was 2.7%, including therapies targeting BRAF V600E or RNF43 mutations in two patients each, and ERBB2 mutation in one patient. In conclusion, EGP programmes in patients with advanced CRC are feasible and identify a subset of patients with potentially druggable genomic alterations. However, further efforts must be made to increase the rate of patients treated with genomically guided therapies.