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Abstract Details
. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma
J Hepatol. 2022 Apr;76(4):862-873.doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11
1Department of Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw.
2Department of Medical Oncology, People's Liberation Army Cancer Center, Nanjing, People's Republic of China.
3Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
4Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany.
5Department of Medical Oncology, Gustave Roussy Cancer Center, Villejuif, France.
6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
7Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
8Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
9Department of Chemotherapy, N. N. Blokhin Russian Cancer Research Center, Moscow, Russia.
10Department of Gastroenterology and Hepatology, University Hospital La Croix-Rousse, Lyon, France.
11Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
12Department of Medical Oncology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
13Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA.
14Product Development Safety, Genentech, Inc., South San Francisco, CA, USA.
15Product Development Biostatistics, Genentech, Inc., South San Francisco, CA, USA.
16Product Development Biostatistics, Roche Product Development, Shanghai, People's Republic of China.
17Product Development Medical Affairs, Roche Product Development, Shanghai, People's Republic of China.
18Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Jiahui International Cancer Center, Jiahui Health, Shanghai, People's Republic of China.
19Department of Medicine, Division of Hematology and Oncology, Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: RFinn@mednet.ucla.edu.
Abstract
Background & aims: IMbrave150 demonstrated that atezolizumab plus bevacizumab led to significantly improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib in patients with unresectable hepatocellular carcinoma at the primary analysis (after a median 8.6 months of follow-up). We present updated data after 12 months of additional follow-up.
Methods: Patients with systemic treatment-naive, unresectable hepatocellular carcinoma were randomized 2:1 to receive 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily in this open-label, phase III study. Co-primary endpoints were OS and PFS by independently assessed RECIST 1.1 in the intention-to-treat population. Secondary efficacy endpoints included objective response rates and exploratory subgroup efficacy analyses. This is a post hoc updated analysis of efficacy and safety.
Results: From March 15, 2018, to January 30, 2019, 501 patients (intention-to-treat population) were randomly allocated to receive atezolizumab plus bevacizumab (n = 336) or sorafenib (n = 165). On August 31, 2020, after a median 15.6 (range, 0-28.6) months of follow-up, the median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab plus bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR] 0.66; 95% CI 0.52-0.85; descriptive p <0.001). The median PFS was 6.9 (95% CI 5.7-8.6) and 4.3 (95% CI 4.0-5.6) months in the respective treatment groups (HR 0.65; 95% CI 0.53-0.81; descriptive p < 0.001). Treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 and 72 (46%) of 156 safety-evaluable patients in the respective groups, and treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients.
Conclusion: After longer follow-up, atezolizumab plus bevacizumab maintained clinically meaningful survival benefits over sorafenib and had a safety profile consistent with the primary analysis.
Lay summary: The primary analysis of IMbrave150 showed that atezolizumab plus bevacizumab had significantly greater benefits than sorafenib in patients with advanced hepatocellular carcinoma, but survival data were not yet mature. At this updated analysis done 12 months later, median overall survival was 5.8 months longer with atezolizumab plus bevacizumab than sorafenib, and the severity profile of treatment-related side effects remained similar. These updated results confirm atezolizumab plus bevacizumab as the first-line standard of care for advanced hepatocellular carcinoma.