Atezolizumab plus Bevacizumab versus Sorafenib in the Chinese Subpopulation with Unresectable Hepatocellular Carcinoma: Phase 3 Randomized, Open-Label IMbrave150 Study

Shukui Qin; Zhenggang Ren; Yin-Hsun Feng; Thomas Yau; Baocheng Wang; Haitao Zhao; Yuxian Bai; Shanzhi Gu; Lindong Li; Sairy Hernandez; Derek-Zhen Xu; Sohail Mulla; Yifan Wang; Hui Shao; Ann Lii Cheng

doi:10.1159/000513486

Atezolizumab plus Bevacizumab versus Sorafenib in the Chinese Subpopulation with Unresectable Hepatocellular Carcinoma: Phase 3 Randomized, Open-Label IMbrave150 Study

Liver Cancer. 2021 Jul;10(4):296-308. doi: 10.1159/000513486. Epub 2021 Apr 23.

Authors

Shukui Qin¹, Zhenggang Ren², Yin-Hsun Feng³, Thomas Yau⁴, Baocheng Wang⁵, Haitao Zhao⁶, Yuxian Bai⁷, Shanzhi Gu⁸, Lindong Li⁹, Sairy Hernandez¹⁰, Derek-Zhen Xu⁹, Sohail Mulla¹¹, Yifan Wang⁹, Hui Shao⁹, Ann Lii Cheng¹²

Affiliations

¹ People's Liberation Army Cancer Center, Jinling Hospital, Nanjing, China.
² Liver Cancer Institute and Department of Liver Cancer Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
⁴ Department of Medicine, Haematology, Medical Oncology & Bone Marrow Transplantation Division, Queen Mary Hospital, Hong Kong, China.
⁵ Department of Oncology, General Hospital of Jinan Military Command, Jinan, China.
⁶ Department of Liver Surgery, Peking Union Medical College Hospital, Beijing, China.
⁷ Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
⁸ Radioactive Interventional Department, Hunan Cancer Hospital, Changsha, China.
⁹ Product Development Oncology, Roche (China) Holding Ltd., Shanghai, China.
¹⁰ Medical Affairs, Genentech, Inc., South San Francisco, California, USA.
¹¹ Product Development Biometrics, Hoffmann-La Roche Ltd., Mississauga, Ontario, Canada.
¹² Department of Medical Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan.

Abstract

Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported.

Methods: IMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population.

Results: Of 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25-0.76) and for PFS was 0.60 (95% CI, 0.40-0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2-8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6-4.8) with sorafenib. Grade 3-4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3-4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent.

Conclusion: Clinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.

Keywords: Checkpoint inhibitor; Chinese patients; Immunotherapy; Liver cancer; Overall survival; Programmed death-ligand 1 inhibitor; Systemic treatment.