TACE-HAIC Combined With TKIs and Immunotherapy Versus TACE Alone for Hepatocellular Carcinoma With PVTT

Study Overview
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Brief Summary
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Hepatocellular carcinoma (HCC) is characterized with vascular invasion, particularly of the portal vein, resulting in portal vein tumor thrombus (PVTT) in 10%-40% of HCC patients at the time of HCC diagnosis. The prognosis of these patients is extremely poor.Treatment efficacy and safety using a combined therapy (TACE-HAIC combined with TKIs and PD-1 inhibitors) were compared with TACE alone in treatment of HCC patients with PVTT.

Official Title
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TACE-HAIC Combined With Targeted Therapy and Immunotherapy Versus TACE Alone for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Propensity Score Matching Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: TACE-HAIC
* Procedure: TACE
* Drug: Targeted therapy
* Drug: PD-1 inhibitors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (a) HCC patients with PVTT (Vp1-4) treated by TACE, or the combination therapy (TACE-HAIC combined with TKIs or an PD-1 inhibitors) as initial treatment; (b) age between 18 and 75 years; (c) Child-Pugh A or B liver function; (d) Eastern Cooperative Oncology Group (ECOG) performance status 0-1; (e) adequate hematologic blood counts (white blood cell count >3ⅹ109/L, absolute neutrophil count >1.5ⅹ109/L, platelet count >10ⅹ109/L, hemoglobin concentration >85 g/L); (f) no extrahepatic metastasis. Exclusion Criteria: (a) severe underlying cardiac, pulmonary, or renal diseases; (b) history of a second primary malignant tumor; (c) incomplete medical data; (d) loss to follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Combined therapy group (TACE-HAIC combined with TKIs and PD-1 inhibitors)<br>Patients recieve combined with TKIs and PD-1 inhibitors | Procedure: TACE-HAIC<br>* The TACE-HAIC which was performed using 30 mg/m2 of epirubicin mixed with 2-5 mL lipiodol, followed by pure lipiodol. Then, a catheter was placed and fixed in the tumor feeding artery for the FOLFOX-based chemotherapy infusion at the following dosage: 85 mg/m2 of oxaliplatin infusion for 2 hours; leucovorin, 400 mg/m2 infusion for 2 hours; 400 mg/m2 of 5-FU bolus; and 2400 mg/m2 of continuous 5-FU infusion for 46 hours or 1200mg/m2 of continuous 5-FU infusion for 23 hours, respectively. Repeated TACE-HAIC was performed at intervals of 3-4 weeks.<br>Drug: Targeted therapy<br>* The TKI therapy used in this study were lenvatinib (12 mg/d for bodyweight ⩾ 60 kg or 8 mg/d for bodyweight <60 kg), sorafenib (400 mg twice a day) or apatinib (250-500 mg orally once daily). Administration of lenvatinib, apatinib or sorafenib was started on the first post-TACE day, and continually administered until disease progression developed or serious treatment-related toxicity occurred.<br>Drug: PD-1 inhibitors<br>* PD-1 inhibitors were intravenously administered on the first post-TACE day as follows: camrelizumab 200 mg or sintilimab 200 mg or toripalimab 240 mg or tislelizumab 200 mg, every 3-4 weeks.<br>|
| TACE alone group<br>TACE alone | Procedure: TACE<br>* TACE was performed using 30 mg/m2 of epirubicin, 200 mg/m2 of carboplatin, and 4mg/m2 of MMC, mixed with 2-5 mL lipiodol. Up to 20 mL of additional pure lipiodol were injected into the tumor-feeding artery until stasis of blood flow was observed in the target artery. Repeated TACE was performed at intervals of 3-4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | The tumor responses were evaluated by measuring the longest diameter of target lesions according to response evaluation criteria in solid tumors (RECIST) version 1.1 | 24 months | 
| Overall survival | Overall survival (OS) was measured from the initiation of transarterial therapy to the date of death or the last follow-up. | 24 months | 
| Progression-free survival | Progression-free survival (PFS) was measured from the initiation of transarterial therapy to the time of progression or recurrence or last follow-up. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion rate | Rate of patients underwent hepatic surgery after careful evaluation when an estimated residual liver volume >30-40% could be remained after R0 surgery by 2 experienced surgeons | 24 rates | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, TACE-HAIC, TACE, TKIs, PD-1 Inhibitors