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.
Liu W, Zhang K, et al. • Frontiers in immunology • 2026
In patients with advanced HCC and VP4 portal vein tumor thrombosis, the addition of PD-1 inhibitors to HAIC plus TKIs (triple therapy) was associated with improved tumor response and prolonged survival without an apparent increase in severe treatment-related adverse events.
Key Findings
Results
Triple therapy achieved a significantly higher objective response rate compared to dual therapy after sIPTW adjustment.
ORR was 58.9% with triple therapy vs 31.4% with dual therapy (P = 0.012)
Disease control rate was also higher with triple therapy: 94.8% vs 72.1% (P = 0.003)
PVTT-specific ORR was higher with triple therapy: 49.9% vs 26.5% (P = 0.034)
Tumor response was assessed according to RECIST version 1.1
97 patients were included: 43 in dual therapy and 54 in triple therapy groups
Results
Triple therapy was associated with significantly longer progression-free survival compared to dual therapy.
sIPTW-adjusted median PFS was 7.3 months with triple therapy vs 5.5 months with dual therapy
HR 0.48, 95% CI 0.31–0.75, P = 0.001
Stabilized inverse probability of treatment weighting (sIPTW) was used to minimize selection bias
Median follow-up was 42.3 months
Results
Triple therapy was associated with significantly longer overall survival compared to dual therapy.
sIPTW-adjusted median OS was 14.6 months with triple therapy vs 10.1 months with dual therapy
HR 0.47, 95% CI 0.29–0.74, P = 0.001
This represents a 4.5-month improvement in median OS with the addition of PD-1 inhibitors
Results
Treatment regimen and baseline neutrophil-to-lymphocyte ratio were identified as independent prognostic factors for both PFS and OS.
Identified via multivariable Cox regression analysis
Treatment regimen (dual vs triple therapy) was an independent factor for both PFS and OS
Baseline neutrophil-to-lymphocyte ratio was independently associated with both PFS and OS
Results
Grade 3–4 treatment-related adverse events were comparable between the triple and dual therapy groups.
Grade 3–4 adverse event rates were 35.2% (triple therapy) vs 30.2% (dual therapy), P = 0.606
No treatment-related deaths were reported in either group
The addition of PD-1 inhibitors did not appear to significantly increase severe toxicity
Methods
This was a single-center retrospective cohort study enrolling consecutive treatment-naïve patients with advanced HCC and VP4 PVTT.
Study period: January 2018 to July 2025
97 total patients enrolled: 43 receiving HAIC plus TKIs (dual therapy) and 54 receiving HAIC plus TKIs plus PD-1 inhibitors (triple therapy)
Primary endpoints were ORR, PFS, OS, and safety
sIPTW was applied to minimize selection bias inherent in the retrospective design
What This Means
This research studied patients with a particularly aggressive form of liver cancer (hepatocellular carcinoma, or HCC) that had spread into the main portal vein supplying the liver — a condition called VP4 portal vein tumor thrombosis, which carries a very poor prognosis. Researchers compared two treatment approaches: a combination of regional chemotherapy delivered directly into the liver's artery (HAIC) plus targeted drugs (TKIs), versus that same combination with the addition of immune checkpoint-blocking drugs (PD-1 inhibitors). The study looked at 97 patients treated at a single center over several years and used a statistical technique to make the two groups more comparable despite the non-randomized design.
The study found that patients who received all three types of treatment (HAIC + TKIs + PD-1 inhibitors) had notably better outcomes. Their tumors responded to treatment at a higher rate (about 59% vs 31%), and the cancer was controlled in nearly 95% of triple therapy patients compared to 72% of dual therapy patients. Importantly, patients in the triple therapy group also lived longer without their disease progressing (7.3 vs 5.5 months) and had longer overall survival (14.6 vs 10.1 months). Serious side effects occurred at similar rates in both groups (about 35% vs 30%), and there were no treatment-related deaths in either group.
This research suggests that adding PD-1 immunotherapy drugs to the combination of liver-directed chemotherapy and targeted therapy may meaningfully improve outcomes for patients with this high-risk form of liver cancer, without substantially increasing dangerous side effects. The authors note that these findings come from a retrospective, non-randomized study at a single center, so they call for prospective randomized clinical trials to confirm whether triple therapy should become a standard first-line treatment for this patient population.
Liu W, Zhang K, Chen S, Wang X, Yu W. (2026). 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.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1832313