Abstract
Purpose
The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting.
Methods
Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea).
Results
1312 patients were treated with lenvatinib, and 823 patients were treated with atezolizumab plus bevacizumab. Objective response rate (ORR) was 38.6% for patients receiving lenvatinib, and 27.3% for patients receiving atezolizumab plus bevacizumab (p < 0.01; odds ratio 0.60). For patients who achieved complete response (CR), overall survival (OS) was not reached in both arms, but the result from univariate Cox regression model showed 62% reduction of death risk for patients treated with atezolizumab plus bevacizumab (p = 0.05). In all multivariate analyses, treatment arm was not found to be an independent factor conditioning OS. Comparing ORR achieved in the two arms, there was a statistically significant difference in favor of lenvatinib compared to atezolizumab plus bevacizumab in all subgroups except for Eastern patients, Child–Pugh B patients, presence of portal vein thrombosis, α-feto-protein ≥ 400 ng/mL, presence of extrahepatic disease, albumin–bilirubin (ALBI) grade 2, and no previous locoregional procedures.
Conclusion
Lenvatinib achieves higher ORR in all patient subgroups. Patients who achieve CR with atezolizumab plus bevacizumab can achieve OS so far never recorded in HCC patients. This study did not highlight any factors that could identify patient subgroups capable of obtaining CR.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- HCC:
-
Hepatocellular carcinoma
- ORR:
-
Objective response rate
- CR:
-
Complete response
- OS:
-
Overall survival
- HR:
-
Hazard ratio
- CI:
-
Confidence interval
- PFS:
-
Progression-free survival
- BCLC:
-
Barcelona clinic liver cancer
- PR:
-
Partial response
- FU:
-
Follow-up
- CP:
-
Child–Pugh
- TACE:
-
Trans-arterial chemoembolization
- ECOG:
-
Eastern Cooperative Oncology Group
- SD:
-
Stable disease
- PD:
-
Progressed disease
- ALBI:
-
Albumin–bilirubin
- NLR:
-
Neutrophil–lymphocyte ratio
- αFP:
-
Alpha-feto-protein
- PVT:
-
Portal vein thrombosis
- EHD:
-
Extrahepatic disease
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AC-G, MP, and MR contributed to the study conception and design. Material preparation and data collection were performed by all authors. Analysis and interpretation of data were performed by AC-G, MP, and MR. The first draft of the manuscript was written by AC-G, MP, and MR and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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M.K. has received grants from Taiho Pharmaceuticals, Chugai Pharmaceuticals, Otsuka, Takeda, Sumitomo Dainippon-Sumitomo, Daiichi Sankyo, AbbVie, Astellas Pharma, and Bristol-Myers Squibb; has received grants and personal fees from MSD, Eisai, and Bayer, and is an adviser for MSD, Eisai, Bayer, Bristol-Myers Squibb, Eli Lilly and ONO Pharmaceutical. L.R. has received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel expenses from AstraZeneca; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. F.P. has received consulting or lecture fees from Consulting or lecture fees in the last two years from: Astrazeneca, Bayer, Bracco, EISAI, ESAOTE, Exact Sciences, IPSEN; MSD; Roche, Samsung, Tiziana Life Sciences. M.S. is an advisor for MSD, Eisai, MERCK, SERVIER, and AMGEN. A.C-G. has received grants and personal fees from MSD, Eisai, Bayer, and is an advisor for MSD, Eisai, Bayer, Bristol-Myers Squibb, AstraZeneca and GSK. The other authors have no relevant financial or non-financial interests to disclose.
Ethics statement
Study was approved by Ethics Committee at each center (number of approval code 113/INT/2021 by the IRCCS San Raffaele Hospital Ethic Committee), complied with the provisions of the Good Clinical Practice guidelines and the Declaration of Helsinki and local laws, and fulfilled the Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data.
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Persano, M., Rimini, M., Tada, T. et al. Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study. J Cancer Res Clin Oncol 149, 5591–5602 (2023). https://doi.org/10.1007/s00432-022-04512-1
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DOI: https://doi.org/10.1007/s00432-022-04512-1