Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2–12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child–Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes.

Purpose: Immune checkpoint inhibitors are effective therapies for advanced hepatocellular carcinoma (HCC); however, comparisons of the clinical efficacy and safety profile for these drugs are still scarce. Thus, the aims of this study were to investigate the differences in efficacy and safety between nivolumab and pembrolizumab in unresectable HCC patients in a real-world setting. Patients and methods: A total of 115 patients who received treatment with nivolumab (n = 73) or pembrolizumab (n = 42) in combination with or without tyrosine kinase inhibitors was enrolled. Therapeutic response, survival outcomes, and safety profiles were compared among these groups. Multivariate analysis of survival response was performed using Cox proportional hazards regression. Results: Patients treated with pembrolizumab demonstrated a significantly higher objective response rate than those with nivolumab (38.1% vs. 15.1%; odds ratio 4.18, p = 0.005) regardless of the combination strategies. In addition, pembrolizumab performed a better overall survival (OS) than nivolumab, (34.9 vs. 9.5 months; hazard ratio (HR) = 0.39, p = 0.004). In subgroup analysis, pembrolizumab exhibited favorable OS than nivolumab for monotherapy (HR = 0.16, p = 0.001) or combination therapy (HR = 0.33, p = 0.006) as second-line or later-line (HR = 0.19, p = 0.001) therapy and those with (HR = 0.31, p = 0.006) or without (HR = 0.15, p = 0.004) well-compensated liver disease. The incidence of adverse events was comparable for both treatments. Conclusion: Both pembrolizumab and nivolumab had significant effects for HCC therapy, and pembrolizumab had a significant survival benefit as compared with nivolumab.

Background: The presence of vascular invasion is associated with poor survival in advanced hepatocellular carcinoma (HCC). We compared the effectiveness of hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs), alone or in combination, in patients with advanced HCC. Methods:We retrospectively reviewed medical records of adult patients with unresectable HCC and macrovascular invasion (MVI) who were treated with HAIC or ICIs alone or in combination at a single centre in Taiwan. Overall tumour response, vascular thrombi response, overall survival (OS) and progressionfree survival (PFS) in 130 patients were analysed. Results:The treatment group showed no significant effect on the overall tumour response [objective response rate (ORR), 22.86% for HAIC, 26.09% for ICI, 50.00% for HAIC+ICI; P=0.111], but showed a significant effect on vessel response (objective response rate of tumour thrombi (ORRT), 38.57% for HAIC, 45.65% for ICI, 78.57% for HAIC+ICI; P=0.023). Post-hoc comparisons followed by Bonferroni correction revealed that vessel ORRT was significantly different between the HAIC+ICI and HAIC groups (P=0.014). A significant effect of treatment group on portal vein tumour thrombus (PVTT) was also detected (ORRT, 40.00% for HAIC, 50.00% for ICI, 90.00% for HAIC; P=0.013), with significant difference between the HAIC+ICI and HAIC groups (P=0.005). Patients treated with HAIC, ICI, and HAIC+ICI respectively had 12-month OS rates of 44.9%, 31.4%, and 67.5% (P=0.127) and 12-month PFS rates of 21.2%, 24.6%, and 33.2% (P=0.091). In multivariate analysis of PFS, HAIC+ICI was associated with reduced risk of progression or death compared with HAIC alone (adjusted hazard ratio: 0.46; 95% confidence interval: 0.23-0.94; P=0.032).Conclusions: HAIC combined with ICIs had a superior response of PVTT compared to HAIC alone, and was associated with reduced risk of progression or death. Future studies are needed to address the survival benefit of the combination therapy in advanced HCC with MVI.