AIM: Although several therapeutic agents show efficacy in advanced hepatocellular carcinoma (HCC), biomarkers such as comprehensive genomic profiling (CGP) for the selection of second-line treatments after immunotherapy have not been established. We evaluated the value of CGP for the treatment decision in patients with HCC. METHODS: We retrospectively studied 52 patients with advanced HCC who received CGP tests at three tertiary hospitals between February 2022 and November 2023. Genomic profiles were obtained using one of three CGP tests
49 and 3 patients were evaluated using tissue-based and blood-based assay, respectively. The impact of CGP results on subsequent treatment selection in clinical practice and correlations between representative gene alterations and patient characteristics or responses to immunotherapy were evaluated. RESULTS: The most frequently observed variants were TERT mutations, followed by CTNNB1, TP53, ARID1A, and MYC mutations. Potentially druggable gene alterations were observed in 45 patients (87%), and 34 patients (65%) were recommended to receive treatments based on specific gene alterations by a molecular tumor board. Treatments were covered by health insurance in 13 patients (25%). Five patients (10%) received the recommended treatment by the date of data cut-off. There were no differences in the efficacy of immunotherapy with respect to mutation status in hTERT, CTNNB1, TP53, ARID1A, and MYC. CONCLUSIONS: The results of the present study suggested that druggable gene alterations may provide useful information not only in proposing alternative treatment after standard of care but also in selecting second-line targeted treatments after immunotherapy for patients with advanced HCC.