Therapeutic impact and timing of gastrointestinal malignancy genomic profiling: A single-institution experience.

Abstract

584 Background: Tumor genomic profiling has become critical in the identification of targeted therapeutic options for patients (pts) with advanced malignancies. Mutational frequencies and their therapeutic importance vary among tumor types. This analysis was undertaken to characterize the landscape of genomic alterations in gastrointestinal (GI) malignancies found in a large academic institutional practice, and to determine the frequency of alteration-specific targeted therapy selection based on genomic profiling. Methods: Adult pts with GI malignancies presenting to the Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing through FoundationOne testing as part of routine clinical care. Institutional review board approval was obtained to retrospectively analyze results from FoundationOne testing performed between 2012 and 2015. Results: 265 pts with GI malignancies underwent successful genomic profiling. 1205 genomic alterations were found, with an average of 4.5 per tumor (range 0-20); 365 (30%) of these were potentially actionable and most often found in colorectal or gastroesophageal tumors. 14 pts (5.3%) had actionable alterations in MET, CDKN2A/B, FGFR2, KRAS, BRAF, or NF2 that led to enrollment in genotype-directed clinical trials or off label use of targeted therapies beyond standard of care. Pt performance status at the time of genomic alteration identification was a significant factor in precluding genotype-directed therapy. One variant of unknown significance involving FGFR2 identified at initial testing subsequently became actionable and led to pt enrollment on a clinical trial. One pt with rectal cancer was found to have a KRAS wild-type and BRAF mutant primary but KRAS mutant and BRAF wild-type liver metastasis. Conclusions: Genomic profiling of GI malignancies through next generation sequencing is feasible and can lead to genotype-directed therapy selection; however, it should be considered early in the pt’s course to optimize use of targeted therapies through clinical trials. Consideration should be given to serial tumor testing to identify emerging genomic alterations for optimal therapy selection.