Next-generation sequencing (NGS) in metastatic gastrointestinal cancer (mGIC) patients: Translation from sequence data into clinical practice.

Abstract

72 Background: A considerable number of patients with mGIC progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with the use of a NGS platform in refractory mGIC and its clinical utility. Methods: We retrospectively reviewed demographics, NGS results, and the suggested therapies received by patients undergoing NGS (Foundation Medicine, Cambridge, MA, USA): exonic sequencing of 236 genes and selective intronic sequencing from 19 genes for refractory mGIC. Co-primary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage of them who received genotype-directed therapy. Results: Samples from 32 patients were tested. Primary tumors consisted of colorectal adenocarcinoma (37,5%), pancreatic adenocarcinoma (31,2%), gastric adenocarcinoma (12,5%), cholangiocarcinoma (12,5%) and hepatocellular carcinoma (6%). Most patients (87,5%) were found to harbor potentially actionable genetic alterations involving mitogen-activated protein kinase (93,7%), phosphatidylinositol 3-kinase-AKT (18,7%), p53 (50%) and cell-cycle regulation (9%) pathways. Of the 6 patients who received the suggested targeted therapy, 4 achieved an objective response. Conclusions: Mutational profiling using a targeted NGS panel identified potentially actionable alterations in the majority of advanced gastrointestinal cancer patients. The assay provided clinical benefit in 12% of the patients.