Clinical Utility of Comprehensive Genomic Profiling in Patients with Unresectable Hepatocellular Carcinoma

Abstract

This study aimed to investigate the clinical usefulness of comprehensive genomic profiling (CGP) in patients with unresectable hepatocellular carcinoma who received multiple systemic therapies in real-world practice. In this study, all nine patients had gene alterations, and seven were candidates eligible for clinical trials based on the results of CGP. The median number of alterations per patient was four, and the blood sample was used in five patients with extrahepatic metastasis. We revealed the genomic information of the patients who received multiple systemic therapies and reported the utility of blood samples in patients with extrahepatic metastasis. Furthermore, the genomic status in patients treated with multiple molecular-targeted agents, including checkpoint inhibitors, would contribute to developing newer systemic agents. The molecular mechanism of hepatocellular carcinoma (HCC) is partially demonstrated. Moreover, in the patients receiving multiple molecular-targeted therapies, the gene alternations are still unknown. Six molecular-targeted therapies of unresectable HCC (uHCC) and comprehensive genomic profiling (CGP) have been approved in clinical practice. Hence, the utility of CGP in patients with uHCC treated with multiple molecular-targeted agents is investigated. The data of the patients with uHCC who received CGP tests were collected, retrospectively, between February 2021 and May 2022. Gene alterations detected by foundation testing, excluding variants of unknown significance, were reported in all nine patients. The samples for CGP were derived from liver tumor biopsy (n = 2), surgical specimens of bone metastases (n = 2), and blood (n = 5). The median number of systemic therapies was four. Seven patients were candidates eligible for clinical trials. One patient with a high tumor mutation burden (TMB) could receive pembrolizumab after CGP. This study presented genomic alternations after receiving multiple molecular-targeted therapies. However, further investigation needs to be conducted to develop personalized therapies and invent newer agents for treating HCC.