Ann-Lii Cheng1, Shukui Qin2, Masafumi Ikeda3, Peter R Galle4, Michel Ducreux5, Tae-You Kim6, Ho Yeong Lim7, Masatoshi Kudo8, Valeriy Breder9, Philippe Merle10, Ahmed O Kaseb11, Daneng Li12, Wendy Verret13, Ning Ma14, Alan Nicholas15, Yifan Wang16, Lindong Li17, Andrew X Zhu18, Richard S Finn19. 1. Department of Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw. 2. Department of Medical Oncology, People's Liberation Army Cancer Center, Nanjing, People's Republic of China. 3. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 4. Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany. 5. Department of Medical Oncology, Gustave Roussy Cancer Center, Villejuif, France. 6. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. 7. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 8. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan. 9. Department of Chemotherapy, N. N. Blokhin Russian Cancer Research Center, Moscow, Russia. 10. Department of Gastroenterology and Hepatology, University Hospital La Croix-Rousse, Lyon, France. 11. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 12. Department of Medical Oncology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA. 13. Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA. 14. Product Development Safety, Genentech, Inc., South San Francisco, CA, USA. 15. Product Development Biostatistics, Genentech, Inc., South San Francisco, CA, USA. 16. Product Development Biostatistics, Roche Product Development, Shanghai, People's Republic of China. 17. Product Development Medical Affairs, Roche Product Development, Shanghai, People's Republic of China. 18. Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Jiahui International Cancer Center, Jiahui Health, Shanghai, People's Republic of China. 19. Department 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. GOV IDENTIFIER: NCT03434379. 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.
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. GOV IDENTIFIER: NCT03434379. 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.
Authors: Osman Öcal; Kerstin Schütte; Christoph J Zech; Christian Loewe; Otto van Delden; Vincent Vandecaveye; Chris Verslype; Bernhard Gebauer; Christian Sengel; Irene Bargellini; Roberto Iezzi; Alexander Philipp; Thomas Berg; Heinz J Klümpen; Julia Benckert; Maciej Pech; Antonio Gasbarrini; Holger Amthauer; Peter Bartenstein; Bruno Sangro; Peter Malfertheiner; Jens Ricke; Max Seidensticker Journal: Eur J Nucl Med Mol Imaging Date: 2022-08-02 Impact factor: 10.057
Authors: Josep M Llovet; Roser Pinyol; Robin K Kelley; Anthony El-Khoueiry; Helen L Reeves; Xin Wei Wang; Gregory J Gores; Augusto Villanueva Journal: Nat Cancer Date: 2022-04-28