Marked Response to Nivolumab Plus Ipilimumab After the Failure of Two Prior Immune Checkpoint Inhibitor-Based Regimens Including CTLA-4 Blockade in Advanced Hepatocellular Carcinoma.

Immune checkpoint inhibitor (ICI)-based combination therapies are standard treatments for advanced hepatocellular carcinoma (HCC). However, the efficacy of sequential ICI regimens remains unclear. We report the case of a 59-year-old woman with advanced HCC with peritoneal dissemination who showed rapid tumor regression after nivolumab plus ipilimumab as a third ICI-based regimen, following confirmed progression on durvalumab plus tremelimumab and atezolizumab plus bevacizumab. After two cycles, tumor markers markedly decreased, and radiological evaluation demonstrated a partial response by Response Evaluation Criteria in Solid Tumors (RECIST) and a complete response by modified RECIST (mRECIST). By late May 20XX+2, the patient had completed four cycles of nivolumab plus ipilimumab without any additional adverse events. The marked biochemical response was maintained, with alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels further decreasing to 173.6 ng/mL and 76 mAU/mL, respectively. The patient is currently scheduled for a follow-up radiological evaluation to confirm the durability of the response. This case suggests that nivolumab combined with ipilimumab may retain efficacy even after multiple prior ICI failures.