Immune Checkpoint Inhibitors and Anti-vascular Endothelial Growth Factor Antibody/Tyrosine Kinase Inhibitors With or Without HAIC for Unresectable HCC With Portal Vein Tumor Thrombosis

Anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors (VEGF/TKI-ICI) plus Immune checkpoint inhibitors (ICIs) are recommended for patients with unresectable hepatocellular carcinoma (HCC) with PVTT in China. However, these treatments have limited survival benefit in patients with advanced HCC with PVTT. We aimed to investigate whether hepatic arterial infusion chemotherapy (HAIC) in combination with VEGF/TKI-ICI and ICIs could improve the efficacy.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma (HCC)

Detailed Description

The multiple real-world studies have shown that Anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors plus immune checkpoint inhibitors (ICIs) (VEGF/TKI-ICI) does not result in a high response rate or extended survival for patients with extrahepatic metastases, with an objective response rate (ORR) of less than 20%. Therefore, there is an urgent need to explore effective therapeutic strategies that can enhance the combined antitumor efficacy of (VEGF/TKI-ICI) and improve the prognosis of patients with advanced hepatocellular carcinoma (HCC) with PVTT. In addition to VEGF/TKI-ICI, more aggressive treatments, such as hepatic arterial infusion chemotherapy (HAIC), have been adopted in the Asia-Pacific region. HAIC significantly increases drug concentration in HCC tissues while decreasing drug distribution in the peripheral blood, thereby improving intrahepatic tumor control and reducing systemic adverse events (AEs). Recent significant advancements have been reported in both local-regional and systemic therapies. Furthermore, the combination of HAIC with VEGF/TKI-ICI (HAIC-VEGF/TKI-ICI) may provide potential synergistic anticancer activity for HCC based on the following rationale: HAIC can effectively kill tumors while promoting the release of tumor antigens, thus transforming "cold tumors" into "hot tumors." At the same time, VEGF/TKI can reverse the tumor neovascularization induced by interventional therapies and enhance tumor vasculature normalization. However, it remains unclear whether patients with advanced HCC can benefit from HAIC-VEGF/TKI-ICI through intrahepatic lesion control, thereby impeding tumor progression. Accordingly, this national multiple-centers retrospective study aims to compare the clinical benefits and tolerability of HAIC-VEGF/TKI-ICI versus VEGF/TKI-ICI alone.

• Study Type: Observational
• Enrollment (Actual): 1649

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Zhongda hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients with unresectable HCC and PVTT who received HAIC in combination with PD-1/PD-L1 inhibitors and molecular target therapies under real-world practice conditions

Description

Inclusion Criteria:

1. Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
2. Barcelona Clinic Liver Cancer (BCLC) stage C (HCC with PVTT);
3. Has not received any previous systemic therapy for HCC (including chemotherapy, molecularly targeted therapy, immunotherapy);
4. Both PD-1/PD-L1 inhibitors and anti-angiogenesis drugs patients received only include marketed drugs but are not limited to HCC approval;
5. HAIC was performed after the first PD-1/PD-L1 inhibitor/anti-angiogenic drug treatment or before treatment (within 2 months);
6. Received at least 1 cycle of PD-1/PD-L1 inhibitor/anti-angiogenic drug combination therapy after HAIC treatment;
7. Has repeated measurable intrahepatic lesions;

Exclusion Criteria:

1. Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes(confirmed by histology, or pathology) are not eligible;
2. Unable to meet criteria of combination timeframe described above;
3. Child-Pugh C or PS>2 or Severe hepatic encephalopathy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival(OS)	The OS is defined as the time from the initiation of any combination treatment to death due to any cause.	up to approximately 2 years
Progression free survival(PFS) per RECIST 1.1 or mRECIST	The PFS is defined as the time from the initiation of any combination treatment to the first documented progressive disease (according to RECIST 1.1 or mRECIST) or death due to any cause, whichever occurs first.	up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR) per RESCIST 1.1	The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1.	up to approximately 2 years
ORR per mRECIST	The ORR is defined as the proportion of patients with a documented CR or PR per mRECIST.	up to approximately 2 years
Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0	The percentage and degree of patients who experience at least one AE, whether or not considered related to the treatment, according to CTCAE version 5.0.	up to approximately 2 years

Collaborators and Investigators

• Sponsor: Zhongda Hospital
• Investigators: Principal Investigator: Gao-jun Teng, M.D, Zhongda hospital, Southeast university, Nanjing, China

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: March 12, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 18, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; immune checkpoint inhibitors; molecular target therapies; hepatic infusion chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: CHANCE2504

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No