Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial

Qin S 1 , Chen M 2 , Cheng AL 3 , Kaseb AO 4 , Kudo M 5 , Lee HC 6 Show all authors , Yopp AC 7 , Zhou J 8 , Wang L 9 , Wen X 10 , Heo J 11 , Tak WY 12 , Nakamura S 13 , Numata K 14 , Uguen T 15 , Hsiehchen D 16 , Cha E 17 , Hack SP 17 , Lian Q 17 , Ma N 17 , Spahn JH 17 , Wang Y 18 , Wu C 19 , Chow PKH 20 , IMbrave050 investigators

Affiliations 

  • 1 Jinling Hospital of Nanjing University of Chinese Medicine, Nanjing, China
  • 2 Sun Yat-sen University Cancer Center, Guangzhou, China
  • 3 National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
  • 4 The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 5 Kindai University, Osaka, Japan
  • 6 Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
  • 7 Department of Surgery, Division of Surgical Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
  • 8 Zhongshan Hospital, Fudan University, Shanghai, China
  • 9 Fudan University Shanghai Cancer Center, Shanghai, China
  • 10 1st Hospital of Jilin University, Jilin, China
  • 11 College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
  • 12 Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea
  • 13 Himeji Red Cross Hospital, Hyogo, Japan
  • 14 Yokohama City University Medical Center, Yokohama, Japan
  • 15 Hôpital de Pontchaillou, Rennes, France
  • 16 Department of Internal Medicine, Division of Hematology and Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
  • 17 Genentech, South San Francisco, CA, USA
  • 18 Fudan University Shanghai Cancer Center, Shanghai, China; Genentech, South San Francisco, CA, USA
  • 19 Roche (China) Holding, Shanghai, China
  • 20 National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, Singapore. Electronic address: pierce.chow@duke-nus.edu.sg
Lancet, 2023 Nov 18;402(10415):1835-1847.
PMID: 37871608 DOI: 10.1016/S0140-6736(23)01796-8

Abstract

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma.

METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098.

FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab.

INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.

FUNDING: F Hoffmann-La Roche/Genentech.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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