Hepatocellular Carcinoma (HCC)
Conditions
Keywords
hepatocellular carcinoma, immune checkpoint inhibitors, molecular target therapies, hepatic infusion chemotherapy
Brief summary
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.
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.
Interventions
None listed
Sponsors
Zhongda Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival(OS) | up to approximately 2 years | The OS is defined as the time from the initiation of any combination treatment to death due to any cause. |
| Progression free survival(PFS) per RECIST 1.1 or mRECIST | up to approximately 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate(ORR) per RESCIST 1.1 | up to approximately 2 years | The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1. |
| ORR per mRECIST | up to approximately 2 years | The ORR is defined as the proportion of patients with a documented CR or PR per mRECIST. |
| Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0 | up to approximately 2 years | 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORGao-jun Teng, M.D
Zhongda hospital, Southeast university, Nanjing, China
Outcome results
None listed