Efficacy of Cabozantinib and Nivolumab in Treating Hepatocellular Carcinoma with RET Amplification, High Tumor Mutational Burden, and PD-L1 Expression.

We report on a patient with hepatocellular carcinoma (HCC) who developed bone metastasis after surgery. RET amplification, high tumor mutational burden (TMB; TMB ≥10 mutations per megabase), and programmed death-ligand 1 (PD-L1) expression were detected by next-generation sequencing. Oral administration of cabozantinib was initiated. Nivolumab was added after 1 month. The patient responded well to cabozantinib and nivolumab therapy, with tolerated adverse reactions, and achieved progression-free survival of more than 25 months. To the best of our knowledge, this is the first clinical case report in the literature to describe the benefit of cabozantinib and nivolumab treatment in a patient with HCC and RET amplification, high TMB, and positive PD-L1 expression. This study explored the selection of biomarkers for targeted therapy and combination immunotherapy in patients with HCC. KEY POINTS: A patient with metastatic hepatocellular carcinoma (HCC) harboring RET amplification, high tumor mutational burden, and positive programmed death-ligand 1 expression responded well to the combination of cabozantinib and nivolumab therapy with progression-free survival of longer than 25 months. The combination of nivolumab and cabozantinib may be a good option for patients with advanced HCC, especially those with bone metastasis. The efficacy of cabozantinib and immune checkpoint inhibitors suggests the necessity of the combined application of multiple detection technologies, including next-generation sequencing and immunohistochemistry, for patients with HCC. This study explored the selection of biomarkers for targeted therapy and combination immunotherapy for patients with HCC.