Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial.

Background: The treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC. The results of the interim analysis are presented in this paper.

Methods: AMETHISTA is a multicenter, phase IIIb, single-arm study evaluating the safety and effectiveness of atezolizumab and bevacizumab in an Italian population of patients with systemic treatment-naive HCC (ClinicalTrials.gov: NCT04487067). The primary objective was safety (incidence of grade 3-5 bleeding/hemorrhages). The main secondary objective was effectiveness.

Results: A total of 152 patients were enrolled and 149 were treated. At the cut-off date, the median observation time was 13.4 months (interquartile range 8.3-15.5 months). The incidence of grade 3-5 bleeding/hemorrhages was 11.4%. Besides, results of other safety endpoints were consistent with the safety profile of atezolizumab plus bevacizumab, and the underlying disease, without any new safety observation. The median OS was 18.2 months (95% confidence interval 15.4 months to not evaluable); the median PFS was 8.5 months (95% confidence interval 7.5-11.2 months).

Conclusion: Results from the interim analysis are consistent with data from the IMbrave150 trial, and further confirm first-line atezolizumab plus bevacizumab as a standard of care for patients with systemic treatment-naive advanced and unresectable HCC.