Determinants of long-term survival from atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma
BACKGROUND: Despite the proven superiority against sorafenib, atezolizumab plus bevacizumab (A+B) lacks long-term efficacy data in unresectable hepatocellular carcinoma (uHCC). This study assessed clinicopathologic factors associated with long-term survival with A+B. METHODS: We analyzed patients receiving first-line A+B within AB-Real, a large multicenter registry across Europe, Asia, and the USA. Long-term survivors (LTS) were defined as patients surviving at 24 months. Landmark survival outcomes and associations between baseline clinicopathologic factors and overall survival (OS) were evaluated. RESULTS: Of 1346 patients enrolled, 1085 with Child-Pugh A and ECOG 0-1 received first-line A+B. The median OS was 19.2 months (95% CI: 17.6-20.9), and 2- and 3-year survival rates were 41.4% and 29.3%. Among 695 patients with adequate follow-up, 190 were classified as LTS. The overall response rate was 24.7%, and long-term survivorship was significantly enhanced in radiologic responders (52.2% vs 8.8%, p < 0.001). Compared to non-LTS, LTS more frequently had ALBI grade 1 liver reserve (64.6% vs 38.5%), less PVI (17.9% vs 36.4%), smaller maximum tumor size (3.8 vs 7.0 cm), and lower AFP (median 23.0 vs 240.8 ng/mL) (all p < 0.001). Notably, nearly half (48.8%) of radiologic responders who did not achieve long-term survival had ≥ 2 adverse baseline features, underscoring that tumor burden and liver reserve remain prognostically relevant even among responders. CONCLUSIONS: AB-Real provides the first global real-world evidence of long-term efficacy of A+B in uHCC. Long-term survivorship is enhanced in radiological responders and strongly associated with pre-treatment tumor factors and liver function.
Authors
- Haripriya Andanamala (ORCID: https://orcid.org/0009-0004-0298-512X)
- Calogero Cammà (ORCID: https://orcid.org/0000-0002-9224-1914)
- Amit G. Singal (ORCID: https://orcid.org/0000-0002-1172-3971)
- Francesco Tovoli (ORCID: https://orcid.org/0000-0002-8350-1155)
- Ciro Celsa (ORCID: https://orcid.org/0000-0002-5662-2162)
- Elena Valenzi (ORCID: https://orcid.org/0009-0002-5006-9535)
- Alessandro Parisi (ORCID: https://orcid.org/0000-0003-4629-7762)
- Johann von Felden (ORCID: https://orcid.org/0000-0003-2839-5174)
- Caterina Vivaldi (ORCID: https://orcid.org/0000-0001-9307-2326)
- Pasquale Lombardi (ORCID: https://orcid.org/0000-0001-6262-2161)
- Bernhard Scheiner (ORCID: https://orcid.org/0000-0002-4904-5133)
- Leonardo Brunetti (ORCID: https://orcid.org/0000-0003-2639-4135)
- Claudia Angela Maria Fulgenzi (ORCID: https://orcid.org/0000-0002-5654-9225)
- Matthias Pinter (ORCID: https://orcid.org/0000-0002-7260-532X)
- Giulia Francesca Manfredi (ORCID: https://orcid.org/0000-0002-2399-5376)
- Martin Schönlein (ORCID: https://orcid.org/0000-0002-1010-0975)
- Mario Pirisi (ORCID: https://orcid.org/0000-0001-9740-0155)
- Bernardo Stefanini (ORCID: https://orcid.org/0000-0003-3800-5678)
- Natascha Roehlen (ORCID: https://orcid.org/0000-0002-6653-8765)
- David Sacerdoti (ORCID: https://orcid.org/0000-0002-4933-7718)
- Fionnuala Crowley (ORCID: https://orcid.org/0000-0001-9101-3912)
- Andrea Dalbeni (ORCID: https://orcid.org/0000-0003-0402-4176)
- Aria Torkpour
- Ryan Po-Ting Lin
- David James Pinato
- Andrea Dondo
- Anwaar Saeed
- Changhoon Yoo
- Naoshi Nishida
- Gianluca Masi
- Peter Robert Galle
- Giuseppe Cabibbo
- Susanna Ulahannan
- Hong Jae Chon
- Thomas U Marron
- Lorenza Rimassa
- Wei-Fan Hsu
- Rohini Sharma
- Chun-Yen Lin
- Neehar Dilip Parkih
- Alessandra Auriemma
- Antonio D'Alessio
- Robert Thimme
- Jaekyung Cheon
- Alessio Cortellini
- Fabio Piscaglia
- Yi-Hsiang Huang
- Masatoshi Kudo
- Brooke Wietharn
- Pei-Chang Lee
Institutions
- Università Cattolica del Sacro Cuore (IT)
- Ulsan College (KR)
- University of Verona (IT)
- Marche Polytechnic University (IT)
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Humanitas University (IT)
- Universität Hamburg (DE)
- University of Freiburg (DE)
- China Medical University (TW)
- Johannes Gutenberg University Mainz (DE)
- University of Michigan (US)
- University Medical Center Freiburg (DE)
- Hammersmith Hospital (GB)
- Agostino Gemelli University Polyclinic (IT)
- Taipei Veterans General Hospital (TW)
- University of Ulsan (KR)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- The University of Kansas Cancer Center (US)
- Mount Sinai Hospital (US)
- University Medical Center Hamburg-Eppendorf (DE)
- Department of Health (ES)
- Linkou Chang Gung Memorial Hospital (TW)
- Azienda USL di Bologna (IT)
- China Medical University Hospital (TW)
- Tisch Hospital (US)
- Oklahoma State University Oklahoma City (US)
- CHA University Bundang Medical Center (KR)
- University of Pittsburgh Medical Center (US)
- Campus Bio Medico University Hospital (IT)
- CHA University (KR)
- IRCCS Humanitas Research Hospital (IT)
- Azienda Ospedaliera Universitaria Pisana (IT)
- Imperial College London (GB)
- Medical University of Vienna (AT)
- The University of Texas Southwestern Medical Center (US)
- University of Palermo (IT)
- Kindai University (JP)
- University of Bologna (IT)
Publication Details
- Journal
- European Journal of Cancer
- Published
- 2026-04-16
- DOI
- https://doi.org/10.1016/j.ejca.2026.116749
- Primary Topic
- Hepatocellular Carcinoma Treatment and Prognosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust