Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: An international study.

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. 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. 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. 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.