Successful Treatment of Nivolumab Plus Ipilimumab After Progression on Durvalumab Plus Tremelimumab in Advanced Hepatocellular Carcinoma: A Case Report

Dual immune checkpoint inhibitor (ICI) regimens used to treat advanced hepatocellular carcinoma (HCC) include durvalumab plus tremelimumab and nivolumab plus ipilimumab, but optimal sequencing after progression on the former remains unclear, especially when VEGF-targeted options are limited by comorbidities. A 70-year-old man with chronic kidney disease and proteinuria had unresectable recurrent HCC. He underwent proton beam therapy followed by salvage surgery; however, he subsequently developed recurrent disease that was not amenable to further surgical resection. Durvalumab plus tremelimumab was chosen as first-line systemic therapy owing to contraindications to bevacizumab and tyrosine kinase inhibitors. After two months, CT showed progressive nodal disease with new right-sided pleural dissemination and malignant effusion; the response was progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Therefore, nivolumab plus ipilimumab was commenced as subsequent systemic therapy. After two cycles, he developed grade 2 dermatitis, which was managed with topical corticosteroids. A CT scan revealed a reduction in nodal and pleural lesions, as well as a significant decrease in effusion. At three months, grade 3 immune-mediated colitis required hospitalization; intravenous corticosteroids followed by infliximab led to recovery. ICIs were not reintroduced, and no radiologic progression was observed during the subsequent two months.