Atezolizumab Plus Bevacizumab Versus Sintilimab Plus Bevacizumab With TACE and HAIC in Unresectable Hepatocellular Carcinoma

Atezolizumab Plus Bevacizumab Versus Sintilimab Plus Bevacizumab With Transarterial Chemoembolization and Hepatic Arterial Infusion Chemotherapy in Unresectable Hepatocellular Carcinoma: A Multicenter Real-World Study

Systemic therapy is the primary option for managing advanced hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab (A+B) has emerged as the first-choice treatment for advanced HCC(IM brave 150). The ORIENT-32 study, also reported an ORR of 24% for sintilimab plus a bevacizumab biosimilar (S+B) versus 8% for sorafenib, with significantly longer OS and PFS. Based on those therapeutic advantages over sorafenib, both the A+B and S+B regimens were approved as first-line treatment options for advanced HCC in China. These two trials had very similar designs but included different target populations. Our previous studies have demonstrated that a novel treatment approach combining transarterial chemoembolization (TACE) with hepatic arterial infusion chemotherapy (HAIC) has high efficacy in patients with potentially resectable HCC or portal vein tumor thrombus. However, it remains unknown whether combining immune checkpoint inhibitors and macromolecular VEGF-targeted therapy with transvascular local interventions could improve patient prognosis in uHCC.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Atezolizumab combined with Bevacizumab; Procedure: Transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy; Drug: Sintilimab combined with Bevacizumab

• Study Type: Observational
• Enrollment (Actual): 188

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Wei He

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This retrospective real-world study enrolled patients treated in three medical centers in China, including Sun Yat-sen University Cancer Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, and Sun Yat-Sen Memorial Hospital. These patients, diagnosed with treatment-naive uHCC, underwent simultaneous combination TACE-HAIC and A+B or S+B.

Description

Inclusion Criteria:

• (a) a confirmed diagnosis of uHCC;
• (b) at least one target lesion evaluable by both RECIST 1.1 and mRECIST criteria;
• (c) Child-Pugh Grade A or B.

Exclusion Criteria:

• (a) previous exposure to other anti-cancer treatments;
• (b) diagnosis of any other primary malignancy;
• (c) significant esophageal varices or observable red wale marks;
• (d) a history of severe cardiac, pulmonary, or renal comorbidities;
• (e) incomplete follow-up records.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ABTH; Atezolizumab plus bevacizumab combined with TACE-HAIC	Drug: Atezolizumab combined with Bevacizumab; Atezolizumab 1200 mg IV d1, Q3W, combined with bevacizumab 15 mg/kg IV d1, Q3W treatment, treatment continued until disease progression, development of intolerable toxic reactions; Procedure: Transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy; The chemoembolization process employed 30 mg/m2 of epirubicin and 2-10 mL of lipiodol. This was followed by FOLFOX-based HAIC, including 85 mg/m2 of oxaliplatin, 400 mg/m2 of leucovorin, and an initial bolus of 400 mg/m2 of 5-FU for 2 h, which was then followed by a sustained infusion of 1200 mg/m2 5-FU for 23 h.
SBTH; Sintilimab plus bevacizumab combined with TACE-HAIC	Procedure: Transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy; The chemoembolization process employed 30 mg/m2 of epirubicin and 2-10 mL of lipiodol. This was followed by FOLFOX-based HAIC, including 85 mg/m2 of oxaliplatin, 400 mg/m2 of leucovorin, and an initial bolus of 400 mg/m2 of 5-FU for 2 h, which was then followed by a sustained infusion of 1200 mg/m2 5-FU for 23 h.; Drug: Sintilimab combined with Bevacizumab; Sintilimab 200 mg IV d1, Q3W, combined with bevacizumab 15 mg/kg IV d1, Q3W treatment, treatment continued until disease progression, development of intolerable toxic reactions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival，PFS	Assessed using the mRECIST criteria, defined as patient survival without tumor progression from the start of randomization to the end of year 2	24 months
objective response rate，ORR	Evaluated according to the criteria for evaluating efficacy in solid tumors (mRECIST and RECIST 1.1)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment-related adverse events, TRAEs	incidence rates of treatment-related adverse events during the study	24 months
overall survival, OS	Defined as the time from the start of randomization to death from any cause	24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2021
• Primary Completion (Actual): July 25, 2023
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• 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; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Bevacizumab; Atezolizumab
• Other Study ID Numbers: B2023-690-01

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