Lenvatinib Plus PD-1 Antibody vs TACE for Intermediate-stage HCC Beyond Up-to-seven Criteria

Lenvatinib Plus Programmed Cell Death Protein-1 (PD-1) Antibody Versus Transarterial Chemoembolization for Intermediate-stage Hepatocellular Carcinoma Beyond Up-to-seven Criteria

The purpose of this study is to evaluate the efficacy and safety of lenvatinib combined with PD-1 antibody compared with transarterial chemoembolization (TACE) for patients with intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria

Transarterial chemoembolization (TACE) is the most widely used palliative treatment for hepatocellular carcinoma (HCC) patients. While a number of studies demonstrate poor effect of TACE for patients with hepatocellular carcinoma staged BCLC A/B especially for those with tumor beyond up-to-seven criteria. Recently, Lenvatinib was proved non-inferior to sorafenib in overall survival in advanced hepatocellular carcinoma, and Programmed Cell Death Protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has evaluated the efficacy and safety of lenvatinib plus PD-1 antibody in intermediate-stage HCC. Thus, the investigators carried out this prospective randomized control to demonstrate the superiority of lenvatinib combined with PD-1 antibody over TACE.

Inclusion Criteria:

• The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
• Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
• Barcelona clinic liver cancer-stage B
• Beyond up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumor [in cm] and the number of tumors)
• Eastern Cooperative Oncology Group performance status of 0 to 1
• No Cirrhosis or cirrhotic status of Child-Pugh class A only
• Not applicable for transarterial chemoembolization, surgical resection, and local ablative therapy.
• The following laboratory parameters:

Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/ L Serum albumin ≥ 30 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3

• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
• Known history of HIV
• History of organ allograft
• Known or suspected allergy to the investigational agents or any agent given in association with this trial.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Evidence of bleeding diathesis.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Known central nervous system tumors including metastatic brain disease