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Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: An international study
Background
The phase III IMbrave150 trial led to the approval of immunotherapy with atezolizumab plus bevacizumab as a new first-line standard of care for patients with advanced hepatocellular carcinoma (HCC). Recent evidence suggests that patients with non-viral etiology might be less responsive to immunotherapy. Therefore, we performed a large multicenter analysis of patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib or sorafenib.
Methods
We performed an analysis of prospectively collected retrospectively analysed data from patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and United Kingdom). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we performed the analysis firstly on the whole population, then we divided the cohort into two groups NASH/NAFLD and non-NASH/NAFLD population.
Results
190 patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population Univariate unweighted Cox regression model showed a 29% reduction in the risk of death for patients on lenvatinib (HR 0.71 95%CI: 0.50-1.06; p = 0.1028) and a 36% reduction in the risk of progression for patients on lenvatinib (HR 0.64; 95%CI: 0.49-0.84; p = 0.0017) for patients on lenvatinib, compared with patients on atezolizumab plus bevacizumab. In NASH-NAFLD population univariate unweighted Cox regression model showed a 54% reduction in the risk of death risk (HR 0.46; 95%CI: 0.25-0.88; p = 0.0181), and a 48% reduction in the risk of progression for patients on lenvatinib (HR 0.52; 95%CI: 0.34-0.80; p = 0.0028) for patients on lenvatinib compared with patients on atezolizumab plus bevacizumab. In non- NASH-NAFLD population univariate unweighted Cox regression model showed a 4% reduction in the risk of death (HR 0.96; 95%CI: 0.60-1.54; p = 0.8862) and a 25% reduction in the risk of progression for patients on lenvatinib compared with patients on atezolizumab plus bevacizumab (HR 0.75; 95%CI 0.52-1.08; p = 0.1300) for patients on lenvatinib, compared with patients on atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed.
Conclusions
The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time a significant survival benefit with lenvatinib compared to atezolizumab plus bevacizumab, in particular in patients with NASH/NAFLD-related HCC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
L. Rimassa: Honoraria (self): Lecture fees: AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; Advisory / Consultancy: 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; Research grant / Funding (institution): Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. M. Kudo: Honoraria (self): Bayer AG, Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., Roche; Advisory / Consultancy: Bayer AG, Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., Roche; Research grant / Funding (institution): Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., EA Pharma, Taiho Pharmaceutical, Eisai Co. Ltd., Abbvie. C. Yoo: Honoraria (self): Ipsen, Servier, Eisai, Bayer, AstraZeneca, Roche, Novartis; Research grant / Funding (self): Ipsen, Servier, Bayer, AstraZeneca. All other authors have declared no conflicts of interest.
