Utility of next-generation sequencing in clinical decision making in hepatocellular carcinoma (HCC).

Abstract

295 Background: HCC is a heterogeneous disease with diverse genomic alterations. The prior genomic studies have identified common alterations in TERT, P53, WNT pathways. However, most of these alterations are not targetable with current FDA approved targeted agents. In this study, we determine the clinical impact of targeted next generation sequencing in patients with advanced HCC. Methods: We retrospectively assessed all patients with gastrointestinal (GI) malignancies who have undergone next generation sequencing (NGS) between January 2013 and August 2017. The primary endpoint is to determine the frequency of clinically actionable mutations in HCC. Secondary endpoint is to identify number of patients eligible for current FDA approved targeted agents. Results: Of the 299 consecutive GI tumors sequenced, 29 cases were identified as HCC. Clinically actionable mutations were noted in 22 of 29 patients (pts) (76%). Most pts (52%) were found to harbor more than one potentially actionable genetic alterations (n = 15). The common pathways involved: P53 in 9 pts (22%), cell-cycle regulation in 7 pts (17.1%) and mitogen-activated protein kinase in 6 pts (14.6%). Other pathways involved were DNA repair in 4 pts (9.8%), WNT in 3 pts (7.3%), MYC in 3 pts (7.3%), NOTCH in 2 pts (4.9%), HNPCC in 2 pts (4.9%), APC in 2 pts (4.9%), phosphatidylinositol 3-kinase-AKT-mTOR in 1 patient (pt) (2.4%), BRINP in 1 pt (2.4%) and angiogenesis in 1 pt (2.4%). We noted 10 pts (34.5%) harbor alterations that could potentially be targeted with FDA approved treatments such as palbociclib (for CCND1/2 amplification), PARP inhibitors (for DNA repair defects), and immunotherapy (for MMR defects) on precision medicine clinical trials such as TAPUR or MATCH. Conclusions: Mutational profiling using a targeted NGS panel identified clinically actionable alterations in nearly 75% of advanced HCC patients. Almost one third of these patients were potential candidates for current FDA approved treatments. NGS and enrollment in clinical trials should be considered in all fit patients with HCC who had progression on current standard of care treatments.