Impact of Immune Checkpoint Inhibitors with or without a Combination of Tyrosine Kinase Inhibitors on Organ-Specific Efficacy and Macrovascular Invasion in Advanced Hepatocellular Carcinoma

The tumor microenvironments of different organs often differ and thus may affect the immunotherapy response.This study elucidated that the efficacy of programmed cell death protein-1 (PD-1) inhibitors varies across different metastatic sites among individuals with advanced hepatocellular carcinoma (HCC).We retrospectively analyzed treatment outcomes in advanced HCC patients receiving PD-1 inhibitors with or without a combination of tyrosine kinase inhibitors (TKIs). Both the overall response rate (ORR) and organ-specific response rate (OSRR) were assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A survival analysis and its predictors were determined using a multivariate analysis.We analyzed 42 advanced HCC patients (median age: 58.0 years; 78.6% males). Thirty (71.4%) patients were sorafenib-experienced and 27 (64.3%) were administered a combination of TKIs. The ORR was 14.3% and the disease control rate was 33.3%. The median overall survival (OS) and progression-free survival (PFS) were 12.0 and 2.9 months, respectively. The OSRRs were 14.7, 23.8, 28.6, and 50.0% for the liver, lungs, lymph nodes, and vascular response, respectively. The multivariate analysis indicated that the vascular response was significantly associated with PFS. ECOG performance status was a significant independent predictor of OS.PD-1 inhibitors improved OS and PFS in advanced HCC patients. Their efficacies varied among the metastatic locations regardless of the combination of TKIs; in particular, a higher response in vascular metastases was correlated with a longer PFS. PD-1 inhibitors may deliver a synergistic benefit in patients undergoing traditional therapy and progression in other organs in vascular responders.