Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma

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.

Keywords: PD-L1 inhibitor; advanced hepatocellular carcinoma; combination treatment; first-line systemic treatment; overall survival; survival benefit.

Conflict of interest statement

Conflicts of interest All authors received support from F. Hoffmann-La Roche/Genentech during the conduct of this study. ALC has received honoraria from AstraZeneca, Bristol Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, IPSEN Innovation, Bayer Healthcare, MSD, F. Hoffmann-La Roche/Genentech, BeiGene, CSR Pharma Group, and IQVIA; advisory/consulting fees from AstraZeneca, Bristol Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix, IPSEN Innovation, Bayer Healthcare, MSD, Roche/Genentech, BeiGene, CSR Pharma Group, F. Hoffmann-La Roche, and IQVIA; speaker bureau fees from Bayer Yakuhin, Novartis, Eisai, Ono Pharmaceutical, and Amgen Taiwan; and travel and accommodation expenses from Bayer Yakuhin, F. Hoffmann-La Roche/Genentech, and IQVIA. SQ has no further interests to declare. MI has received institutional grant support Bayer, Eisai, Eli Lilly Japan, Chugai Pharmaceutical, AstraZeneca, MSD, Novartis, Bristol Myers Squibb, and Merck Serono; honoraria from Bayer, Eisai, Eli Lilly Japan, Chugai Pharmaceutical, and Sumitomo Dainippon Pharma, and Takeda; and had a consulting or advisory role for Bayer, Eisai, Eli Lilly Japan, Chugai Pharmaceutical, and Takeda. PRG has had a consulting or advisory role and received honoraria from AdaptImmune, AstraZeneca, Bayer, Bristol Myers Squibb, MSD, Eisai, Lilly, Ipsen, Roche, and Sirtex; has been on a speakers’ bureau for AstraZeneca, Bayer, Bristol Myers Squibb, MSD, Eisai, Lilly, Ipsen, Roche, and Sirtex; has received research funding from Bayer and Roche; has provided expert testimony for Lilly; and has received travel and accommodation expenses from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Lilly, Ipsen, and F. Hoffmann-La Roche. MD has received honoraria and advisory/consultancy fees from F. Hoffmann-La Roche, Merck Serono, Bayer, Ipsen, Servier, Amgen, MSD, and Pierre Fabre; research funding from F. Hoffmann-La Roche, Merck Serono, and Bayer; and travel and accommodation expenses from F. Hoffmann-La Roche, MSD, and Servier. TYK reports grants and nonfinancial support from F. Hoffmann-La Roche. HYL has received advisory/consulting fees from Bayer, Eisai, Bristol Myers Squibb, Ono, AstraZeneca, and F. Hoffmann-La Roche. MK has received honoraria from Lilly, Bayer, Eisai, MSD, Bristol Myers Squibb, and EA Pharma; had a consulting or advisory role for Eisai, Ono, MSD, Bristol Myers Squibb, and F. Hoffmann-La Roche; and received research funding from Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, EA Pharma, AbbVie, and Eisai. VB has received advisory/consultancy fees from F. Hoffmann-La Roche, MSD, Eisai, Bristol Myers Squibb, and Ipsen; and travel and accommodation expenses from F. Hoffmann-La Roche, MSD, Eisai, Bristol Myers Squibb, and Bayer. PM has had a consulting or advisory role for Bayer, Ipsen, Lilly, Eisai, AstraZeneca, Bristol Myers Squibb, and MSD; received institutional research funding from Ipsen; and travel and accommodation expenses from Bayer and Ipsen. AOK has received research support from F. Hoffmann-La Roche, Bristol Myers Squibb, Exelixis, Bayer, AdaptImmune, Immatics, Merck, and Eisai; and advisory/consultancy fees from AstraZeneca. DL has received honoraria and advisory/consultancy fees from Lexicon, Ipsen, Eisai, Exelixis, Advanced Accelerator Applications, Coherus, Sun Pharma, Bayer, Genentech, Taiho, QED, Merck, Adagene, and TerSera; and received institutional research funding from Brooklyn Immunotherapeutics and AstraZeneca. WV, NM, and AN are full-time employees of and hold shareholder or stock options in Genentech. YW and LL are full-time employees of Roche (China) Holding Ltd. AXZ has had a consulting or advisory role for AstraZeneca, Bayer, Eisai, Exelixis, Gilead Sciences, Lilly, Merck, Roche/Genentech, and Sanofi/Aventis; and received institutional research funding from Bayer, Bristol Myers Squibb, Lilly, Merck, and Novartis. RSF has had a consulting or advisory role for and received consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Exelixis, F. Hoffmann-La Roche/Genentech, Lilly, Merck, Novartis, and Pfizer; has received institutional research funding from Bayer, Bristol Myers Squibb, Eisai, Lilly, Merck, Novartis, Pfizer, and F. Hoffmann-La Roche/Genentech; has provided expert testimony for Novartis; and participated on a data safety monitoring board or advisory board for AstraZeneca and Hengrui. Please refer to the accompanying ICMJE disclosure forms for further details.

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