Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab

Chiun Hsu; Michel Ducreux; Andrew X Zhu; Shukui Qin; Masafumi Ikeda; Tae-You Kim; Peter R Galle; Richard S Finn; Ethan Chen; Ning Ma; Youyou Hu; Lindong Li; Ann-Lii Cheng

doi:10.1159/000525499

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab

Liver Cancer. 2022 Aug 25;12(1):44-56. doi: 10.1159/000525499. eCollection 2023 Feb.

Authors

Chiun Hsu^{1

2

3}, Michel Ducreux⁴, Andrew X Zhu^{5

6}, Shukui Qin⁷, Masafumi Ikeda⁸, Tae-You Kim⁹, Peter R Galle¹⁰, Richard S Finn¹¹, Ethan Chen¹², Ning Ma¹³, Youyou Hu¹⁴, Lindong Li¹⁵, Ann-Lii Cheng^{2

3}

Affiliations

¹ Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
² Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
³ Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Medical Oncology, Gustave Roussy Cancer Center, Paris-Saclay University, Villejuif, France.
⁵ Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Jiahui International Cancer Center, Jiahui Health, Shanghai, China.
⁷ Department of Medical Oncology, Jinling Hospital Cancer Center, Nanjing, China.
⁸ Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
⁹ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
¹⁰ Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany.
¹¹ Division of Hematology Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
¹² Product Development Safety, Roche (China) Holding Ltd, Shanghai, China.
¹³ Product Development Safety, Genentech, Inc., South San Francisco, California, USA.
¹⁴ Biostatistics, F. Hoffmann-La Roche, Basel, Switzerland.
¹⁵ Product Development, Roche (China) Holding Ltd, Shanghai, China.

Abstract

Introduction: In the Phase 3 IMbrave150 trial (NCT03434379), atezolizumab + bevacizumab demonstrated a clinically meaningful survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (HCC), including those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. We used IMbrave150 data to investigate the safety and risk of viral reactivation or flare in infected patients treated with atezolizumab + bevacizumab or sorafenib.

Methods: Patients with unresectable HCC not previously treated with systemic therapy were randomized 2:1 to atezolizumab + bevacizumab or sorafenib. In this exploratory analysis, safety was continually evaluated, including for hepatic adverse events. Patients were monitored for HBV and HCV reactivation and flare at screening, the beginning of Cycles 5 and 9, and at treatment discontinuation.

Results: Of 501 enrolled patients, 485 were included in the safety population; 329 (68%) received atezolizumab + bevacizumab, and 156 (32%) received sorafenib. Overall, 150 (31%) and 58 (12%) patients had HBV and HCV infections, respectively. The safety profiles of atezolizumab + bevacizumab and sorafenib were consistent across patients, regardless of viral infection. Overall, hepatic serious adverse events occurred in 11% of patients receiving atezolizumab + bevacizumab and 8% receiving sorafenib. HBV or HCV reactivation occurred in 2% or 16% of atezolizumab + bevacizumab-treated patients, respectively, versus 7% or 14% with sorafenib. There were no instances of hepatitis flare with atezolizumab + bevacizumab.

Conclusions: Atezolizumab + bevacizumab had a similar hepatic safety profile in patients with and without HBV or HCV infection. Viral reactivation rates were similar between arms. Overall, these data support the use of atezolizumab + bevacizumab in patients with HCC and HBV or HCV infection without any special precaution.

Keywords: Atezolizumab; Bevacizumab; Post hoc analysis; Viral flare; Viral reactivation.

Grants and funding

This study is sponsored by F. Hoffmann-La Roche Ltd.