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

4069 Background: Recently, several evidences have suggested that patients with a no-viral hepatocellular carcinoma (HCC) might be less responsive to immunotherapy and more response to Lenvatinib. Methods: The study population derived from prospectively collected retrospectively analyzed data of patients treated with atezolizumab plus bevacizumab (AB) or lenvatinib (L) or sorafenib (S) as first-line treatment for advanced HCC or intermediate HCC deemed not eligible for loco-regional therapies. The overall cohort included Western and Eastern patient populations from 36 centers located in 4 countries(Italy, Japan, Republic of Korea, and United Kingdom) undergoing treatment with L or AB or with S. The primary endpoint was OS of AB versus L; the secondary endpoints were OS of AB versus S. Results: 569 patients received L, 190 patients received AB and 210 received S. In the whole population OS was 17.8 months (95%CI:15.8-43.8) for patients receiving L, and 12.1 months(95%CI:11.1-16.8)for patients treated with AB (HR 0.71; 95% CI:0.50-1.06; p=0.1028); multivariate analysis for imbalance patients characteristic highlighted that L is an independent prognostic factor for OS (HR 0.65; 95% CI:0.44-0.95; p=0.0268), compared AB. In the population affected by NASH/NAFLD, 254 patients were treated with L and 82 patients were treated with AB. OS was 21.2 months (95% CI:18.4-30.6) for patients receiving L, and 12.2 months (95% CI:10.0-16.8) for patients treated with AB (HR 0.46; 95% CI:0.25-0.88; p = 0.0181); multivariate analysis for imbalance patients characteristic highlighted that L is an independent prognostic factor for OS (HR 0.46; 95% CI:0.26-0.84; p=0.031),compared AB. In the cohort of no viral and no NASH/NAFLD patients, no statistically significant differences were reported in terms of OS between patients treated with L versus AB. All these results were confirmed following propensity score matching analysis. By comparing patients receiving AB versus S, no significant differences were found in terms of OS in the whole population, in the NASH/NAFLD population and in no viral/no NASH/NAFLD population. Conclusions: The present analysis conducted on a large number of non-viral HCC patients showed for the first time a significant survival benefit from lenvatinib over atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.