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

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.

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