P1.22 Next Generation Sequencing (NGS) in the Clinic: The Foundation Medicine Experience with first 200 Cases

Abstract

ABSTRACT Background Next Generation Sequencing (NGS) has proven valuable in the research setting. An increasing number of genomic markers has been identified, leading to more therapies. This number is only going to increase. As well, tumor biopsies are diminishing in size. Advances have made it possible to do NGS on paraffin-embedded tissue. Also, the amount of tissue needed for NGS is decreasing. Foundation Medicine is using a clinical grade NGS platform to analyze routine samples with a high degree of sensitivity and specificity. We report here on our first 212 cases. Methods We reviewed the genomic profiles of the first 212 clinical specimens received by our CLIA lab (Foundation Medicine) and analyzed by our NGS assay (Ross J. ASCO 2011). Our assay consists of 182 genes known altered and 14 genes known rearranged in solid tumors. Genomic alterations were categorized as “actionable”if linked to an approved therapy on or off label (e.g.-ALK rearrangement in lung or breast cancer, respectively), a known or suspected contraindication to a given therapy (e.g.-KRAS G12D in colorectal cancer) or a clinical trial linked to the alteration. Results The first 212 tumor specimens received form the basis of this abstract. 7 samples failed analysis (3%) and 17 had no detectable genomic alterations (8%). Major tumor types included lung (n = 48), breast (n = 39), colorectal (n = 16), ovarian (n = 11), pancreatic (n = 9) and esophageal/gastric (n = 8 ) We reported 542 genomic alterations (mean 2.64 per sample, range 0-7) unequivocally involved in oncogenesis. Of these, 286 were actionable (mean 1.40 per sample, range 0-4). Only 108 of these (38%) would have been detected by current assays (166% increase with NGS). 159 samples had one or more actionable alterations (range 0-4) detected by NGS (78%, 95% CI 771-83%) versus only 84 (41%, 95% CI 34-48%) in whom changes would have been detected by current assays. Conclusions The Foundation Medicine platform identifies an unprecedented number of actionable alterations from routine FFPE samples. This assay serves as a paradigm for improving access to therapies and, increasing enrollment in rationally chosen trials. Planned trials will impact on a number of efficacy endpoints.