ArticleFrontiers in immunology2026
Hepatic arterial infusion chemotherapy plus tyrosine kinase inhibitors with or without PD-1 inhibitors for advanced hepatocellular carcinoma with VP4 portal vein tumor thrombosis: a retrospective cohort study.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
Background: Hepatocellular carcinoma (HCC) with VP4 portal vein tumor thrombosis (PVTT) has a poor prognosis. Although hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 (PD-1) inhibitors shows activity in advanced HCC with PVTT, whether adding PD-1 inhibitors to HAIC plus TKIs improves outcomes specifically in VP4 PVTT remains unclear. Methods: This single-center retrospective study enrolled consecutive treatment-naïve patients with advanced HCC and VP4 PVTT who received HAIC plus TKIs (dual therapy) or HAIC plus TKIs and PD-1 inhibitors (triple therapy) from January 2018 to July 2025. Stabilized inverse probability of treatment weighting (sIPTW) was used to minimize selection bias. Primary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: Ninety-seven patients were included: 43 in the dual therapy group and 54 in the triple therapy group. Median follow-up was 42.3 months. After sIPTW adjustment, triple therapy achieved a higher ORR (58.9% vs 31.4%, P = 0.012) and disease control rate (94.8% vs 72.1%, P = 0.003). PVTT ORR was also higher with triple therapy (49.9% vs 26.5%, P = 0.034). Triple therapy was associated with longer sIPTW-adjusted median PFS (7.3 vs 5.5 months; HR 0.48, 95% CI 0.31-0.75, P = 0.001) and OS (14.6 vs 10.1 months; HR 0.47, 95% CI 0.29-0.74, P = 0.001). Multivariable Cox regression identified treatment regimen and baseline neutrophil-to-lymphocyte ratio as independent prognostic factors for both PFS and OS. Grade 3-4 treatment-related adverse events were comparable (35.2% vs 30.2%, P = 0.606), with no treatment-related deaths. Conclusion: In patients with advanced HCC and VP4 PVTT, the addition of PD-1 inhibitors to HAIC plus TKIs was associated with improved tumor response and prolonged survival without an apparent increase in severe treatment-related adverse events. These findings support triple therapy as a potentially preferred first-line strategy for this high-risk population. Prospective randomized trials are needed to validate these findings.
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