Albumin-Bilirubin Grade Analyses of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study

Masatoshi Kudo; Richard S Finn; Ann-Lii Cheng; Andrew X Zhu; Michel Ducreux; Peter R Galle; Naoya Sakamoto; Naoya Kato; Michitaka Nakano; Jing Jia; Arndt Vogel

doi:10.1159/000529996

Albumin-Bilirubin Grade Analyses of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study

Liver Cancer. 2023 Mar 4;12(5):479-493. doi: 10.1159/000529996. eCollection 2023 Oct.

Authors

Masatoshi Kudo¹, Richard S Finn², Ann-Lii Cheng³, Andrew X Zhu^{4

5}, Michel Ducreux⁶, Peter R Galle⁷, Naoya Sakamoto⁸, Naoya Kato⁹, Michitaka Nakano¹⁰, Jing Jia¹¹, Arndt Vogel¹²

Affiliations

¹ Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
² Division of Hematology and Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³ Department of Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan.
⁴ Harvard Medical School, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁵ Jiahui International Cancer Center, Jiahui Health, Shanghai, China.
⁶ Department of Medical Oncology, Gustave Roussy Cancer Center, Paris-Saclay University, Inserm U1279, Villejuif, France.
⁷ Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany.
⁸ Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan.
⁹ Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹⁰ Chugai Pharmaceutical Ltd, Tokyo, Japan.
¹¹ Hoffmann-La Roche Limited, Mississauga, ON, Canada.
¹² Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Abstract

Introduction: Atezolizumab + bevacizumab showed survival benefit in patients with unresectable hepatocellular carcinoma (HCC) versus sorafenib in the Phase III IMbrave150 study. This exploratory analysis examined the prognostic impact of a baseline albumin-bilirubin (ALBI) score.

Methods: Patients with treatment-naïve unresectable HCC, ≥1 measurable untreated lesion, and Child-Pugh class A liver function were randomized 2:1 to receive atezolizumab 1,200 mg + bevacizumab 15 mg/kg every 3 weeks or sorafenib 400 mg twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed in the intention-to-treat population by ALBI/modified (m)ALBI grade. Time to deterioration (TTD; defined as time to 0.5-point increase from the baseline ALBI score over 2 visits or death) of liver function and safety were investigated.

Results: Of 501 enrolled patients, 336 were randomized to receive atezolizumab + bevacizumab (ALBI grade [G] 1: n = 191; G2: n = 144 [mALBI G2a: n = 72, G2b: n = 72]; missing ALBI grade: n = 1) and 165 to sorafenib (ALBI G1: n = 87; G2: n = 78 [mALBI G2a: n = 37; G2b: n = 41]). Median follow-up was 15.6 months. OS and PFS improved with atezolizumab + bevacizumab versus sorafenib in patients with ALBI G1 (OS HR: 0.50 [95% CI: 0.35, 0.72]; PFS HR: 0.61 [95% CI: 0.45, 0.82]). In patients with ALBI G2 or mALBI G2a or G2b, PFS was numerically longer with atezolizumab + bevacizumab versus sorafenib, but no OS benefit was seen. Median TTD in the intention-to-treat population was 10.2 months (95% CI: 8.0, 11.0) with atezolizumab + bevacizumab versus 8.6 months (95% CI: 6.2, 11.8) with sorafenib (HR: 0.82 [95% CI: 0.65, 1.03]). Safety profiles of atezolizumab and bevacizumab were consistent with previous analyses, regardless of ALBI grade.

Conclusion: ALBI grade appeared to be prognostic for outcomes with both atezolizumab + bevacizumab and sorafenib treatment in patients with HCC. Atezolizumab + bevacizumab preserved liver function for a numerically longer duration than sorafenib.

Keywords: Albumin-bilirubin grade; Atezolizumab; Bevacizumab; Unresectable hepatocellular carcinoma.

Grants and funding

This study was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance was sponsored by Chugai Pharmaceutical Co., Ltd.