The Efficacy and Safety of Donafenib Plus PD-1/L1 Monoclonal Antibodies Plus TACE or HAIC as First-line Treatment for Unresectable Hepatocellular Carcinoma A Multi-center, Retrospective Clinical Study

Official title

The Efficacy and Safety of Donafenib Plus PD-1/L1 Monoclonal Antibodies Plus Transarterial Chemoembolization (TACE) or Hepatic Arterial Infusion Chemotherapy (HAIC) as First-line Treatment for Unresectable Hepatocellular carcinomaA Multicenter, Retrospective Clinical Study

Overview

This is a multicenter, retrospective study planned to enroll patients with unresectable hepatocellular carcinoma (uHCC) who received first-line donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC at 8 sites between June 1, 2021 and November 30, 2024. The study consists of two cohorts: Cohort A consists of patients who received donafenib + PD-1/L1 inhibitor + TACE, and Cohort B consists of patients who received donafenib + PD-1/L1 inhibitor + HAIC, with a planned enrollment of 200 patients per cohort. Relevant data will be collected to evaluate the efficacy and safety of donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC in the treatment of uHCC in real-world clinical practice.

Interventions

• Drug Donafeinib
  Donafenib: 200mg Bid, or follow medical order
• Procedure Transcatheter arterial chemoembolization
  Follow medical order
• Drug PD-1 / PD-L1 monoclonal antibody
  Follow Drug instructions or medical order
• Procedure Hepatic Artery Infusion Chemotherapy
  Follow medical orders

Primary outcome measures

• progression free survival(PFS) [Time frame: Up to approximately 2 year]

Secondary outcome measures (5)

• Objective response rate（ORR） [Time frame: up to approximately 2 years]
• Disease control rate（DCR） [Time frame: up to approximately 2 years]
• Overall Survival (OS） [Time frame: up to approximately 2 years]
• Duration of Response（DOR） [Time frame: up to approximately 2 years]
• Safety（incidence of AEs ） [Time frame: up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Patients with unresectable hepatocellular carcinoma (uHCC) who received donafenib, an anti-PD-1/L1 monoclonal antibody combined with transarterial interventional therapy (TACE or HAIC), with retrievable records in the hospital electronic information system between June 1, 2021 and November 30, 2024.
• Diagnosis of hepatocellular carcinoma confirmed by the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition) clinically or by histology/cytology.
• Age ≥18 years, regardless of sex.
• No prior systemic therapy before the administration of donafenib, anti-PD-1/L1 monoclonal antibody combined with transarterial interventional therapy (TACE or HAIC).
• The maximum interval between the initiation of donafenib, anti-PD-1/L1 monoclonal antibody, and transarterial interventional therapy (TACE or HAIC) does not exceed 8 weeks, and at the time the last of these treatment modalities is initiated, the subject must not have experienced disease progression.
• For patients who have previously undergone hepatectomy, the resection must be R0, and tumor recurrence must have occurred more than 24 months after surgery.
• At least one evaluable lesion (according to RECIST v1.1 criteria).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1.
• Child-Pugh class A or B.
• Adequate major organ function, defined by the following criteria:

Complete blood count (without blood transfusion or use of granulocyte colony-stimulating factor \[G-CSF\] within 14 days prior to screening):

• Hemoglobin ≥90 g/L;
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
• Platelet count ≥75×10⁹/L;

\- Blood biochemistry (without albumin use within 14 days prior to screening):

• Albumin ≥28 g/L;
• Total bilirubin ≤2× upper limit of normal (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5× ULN;
• Alkaline phosphatase (ALP) ≤5× ULN;
• Creatinine ≤1.5× ULN;

\- Coagulation function:

• International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN;
• Activated partial thromboplastin time (APTT) ≤1.5× ULN.

Exclusion criteria

• Incomplete or unavailable patient information data; patient refused follow-up or was lost to follow-up;
• Duration of donafenib, PD-1/L1 monoclonal antibody combined with transarterial intervention therapy was less than 1 month;
• Prior histologically/cytologically confirmed diagnosis of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or other components;
• History of malignancy other than hepatocellular carcinoma, unless meeting the following criteria: a) The patient received potentially curative treatment and there has been no evidence of disease for 5 years; b) Successfully treated resected cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 8 centers

• Sun Yat-sen Memorial Hospital — Guangzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• Zhujiang Hospital of Southern Medical University — Guangzhou
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• Harbin Medical University Cancer Hospital — Harbin
• The Affiliated Hospital of Qingdao University — Qingdao
• Zhong Shan Hospital Fudan University — Shanghai
• Yunnan Cancer Hospital — Kunming

Identifiers

NCT: NCT07724951 · B2026-120

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗