Development and Prospective Validation of a Heterogeneous Treatment Effect-Based Decision Model for Transarterial Chemoembolization Combined With or Without Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma

N/ANot Yet RecruitingNCT07109336

Zhongda Hospital790 enrolled

Overview

Unresectable hepatocellular carcinoma (uHCC) constitutes a significant health burden in the Asia-Pacific (APAC) region, particularly in China, where it is frequently associated with hepatitis B virus (HBV) infection and diagnosed at advanced stages. Transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage hepatocellular carcinoma (HCC), though its effectiveness diminishes in unresectable HCC (uHCC) with intermediate-to-high tumor burden. The IMbrave150 trial established atezolizumab plus bevacizumab (Atezo+Bev) as a superior alternative to sorafenib, demonstrating significant survival advantages in uHCC. Given the marked heterogeneity of intermediate-stage HCC, TACE may not benefit all patients equally. The TALENTACE study investigated on-demand TACE combined with Atezo+Bev versus TACE alone in treatment-naïve uHCC patients with intermediate-to-high tumor burden across China and Japan. Results revealed a statistically significant and clinically meaningful improvement in the primary endpoint, TACE- progression-free survival (PFS), though overall survival (OS) remained immature at the time of analysis. This situation establishes a critical and unmet need for randomized controlled trials (RCTs) combined with extensive real-world evidence (RWE) to facilitate the assessment of individualized treatment heterogeneity and provide precise treatment recommendations in China and select Asia-Pacific regions.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

790

Conditions

HCC - Hepatocellular Carcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * • Aged≥18 years * Initiated first-line Atezo+Bev. * Eligible for TACE treatment or received at least one TACE within ±2 months of Atezo+Bev initiation (before Atezo+Bev start, anytime during Atezo+Bev therapy, or after Atezo+Bev discontinuation). * Clinically or pathologically diagnosed uHCC before or at the initiation of Atezo/Bev.The evidence of being diagnosed as "unresectable" may include but is not limited to below: "Unresectable" or "advanced" directly documented in the medical records History of extrahepatic metastasis as evidenced clinically or by radiology, histology or cytology OR China Liver Cancer (CNLC) Stage IIIb * At least one visit record after the initiation of Atezo+Bev * No prior systemic therapy for HCC, especially immunotherapy * No prior locoregional therapy to the target lesion(s) * At least one measurable untreated lesion * ECOG Performance Status of 0-2 Exclusion Criteria: * • Evidence of extrahepatic spread (EHS) * Participating in interventional clinical trials. * Being a candidate for curative treatments * Any condition representing a contraindication to TACE as determined by the investigators * Active or history of autoimmune disease or immune deficiency * Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding * A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment * Evidence of bleeding diathesis or significant coagulopathy * Missing critical baseline or outcome data

Outcomes

Primary Outcomes

Overall survival

defined as time from index date to death from any cause.

Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcomes

TACE-PFS

defined as the time from index date to untreatable progression or TACE failure/refractoriness or any cause of death, whichever occurs first.

Time frame: From index date to untreatable progression or TACE failure/refractoriness or any cause of death, whichever occurs first, assessed up to 10 months

PFS

defined as the time from index date to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 or mRECIST.

Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months

DoR

defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first).

Time frame: From the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), assessed up to 10 months

TTP

defined as the time from index date to unTACE able progression or TACE failure/refractoriness (as defined above).

Time frame: From index date to unTACE able progression or TACE failure/refractoriness (as defined above), assessed up to 10 months

EHS

defined as the time from index date to the first evidence of Extrahepatic Spread.

Time frame: From index date to the first evidence of Extrahepatic Spread, assessed up to 10 months