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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: TACE-HAIC; Drug: Targeted therapy; Drug: PD-1 inhibitors; Procedure: TACE

• Study Type: Observational
• Enrollment (Actual): 743

Contacts and Locations

Study Locations

• China
  • Guangdong
    • GuangZhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We reviewed data of 743 patients diagnosed as HCC patients with PVTT at Sun Yat-Sen University Cancer Center. 604 patients received TACE, and 139 patients received combination therapy.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Combined therapy group (TACE-HAIC combined with TKIs and PD-1 inhibitors); Patients recieve combined with TKIs and PD-1 inhibitors	Procedure: TACE-HAIC; 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.; Drug: Targeted therapy; 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.; Drug: PD-1 inhibitors; 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.
TACE alone group; TACE alone	Procedure: TACE; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yunfei Yuan

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2021
• Primary Completion (ACTUAL): September 30, 2021
• Study Completion (ACTUAL): June 30, 2022

Study Registration Dates

• First Submitted: September 8, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (ACTUAL): September 10, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: HCC; TACE; PD-1 Inhibitors; TKIs; TACE-HAIC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens, Non-Steroidal; Estrogens; Chlorotrianisene; Immune Checkpoint Inhibitors
• Other Study ID Numbers: B2022-312-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No