Molecular profiling to identify potential therapeutic targets in hepatocellular carcinoma.

471 Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is often diagnosed at an advanced stage with limited effective therapies. The advent of comprehensive genomic molecular profiling has the potential to identify novel therapeutic options in the treatment of HCC. In this descriptive clinical utility study, we evaluated the utility of the Oncotype MAP Pan-Cancer Tissue (MAP) test to identify potential therapeutic options, including clinical trials. Methods: Between October 2018 and October 2020, we identified 41 samples from patients with HCC submitted for MAP testing. The MAP test uses tumor tissue to identify single nucleotide variants, indels, copy number alterations, and select structural variants and fusions by next-generation sequencing (NGS) of a 257 gene panel. Tumor mutational burden and microsatellite instability are also determined. A custom immunohistochemical (IHC) panel is also performed. Results from NGS and IHC are run against a proprietary knowledgebase of genomic and proteomic data that includes FDA approvals, NCCN Recommendations and published biomarker data on potentially targetable alterations. Eligibility for ongoing clinical trials is determined using the NCI database. Results: Of the 41 samples, 37 (90%) met minimum tissue requirements (3mm 2 and 15% tumor cellularity) for DNA sequencing. Of these 37 samples, 36 (97%) were successfully sequenced for NGS testing. Median turnaround time from the date of accessioning to the date of laboratory report was 5 days (interquartile range (IQR) 4-6 days). The most frequently identified genomic variants characterized as pathogenic, or unknown significance, were TP53, CTNNB1 and FAT1 genes. Thirty-two samples (86%) had a genomic alteration that could potentially direct treatment. Six samples (16%) had findings directing to an approved treatment for HCC, 4 (11%) had findings for an approved treatment of a different tumor type, and 22 (59%) had findings for one or more clinical trials. Conclusions: The Oncotype MAP Pan-Cancer Tissue test identified molecular variants that could be used to inform treatment decisions in 86% of HCC samples, including 16% to an approved HCC therapy. The Oncotype MAP test may be considered as another tool in the management of advanced HCC patients.