Analysis of hyperprogressive disease due to atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma

Background: Hyperprogressive disease (HPD) is a phenomenon with greatly accelerated tumor growth and clinical deterioration rates compared to pre-therapy, in patients treated with immune checkpoint inhibitors (ICI). The aim of this study is to clarify the reality of HPD in patients with advanced hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atez/Bev) using tumor dynamics. Methods Medical records of consecutive patients with advanced HCC who were treated with Atez/Bev were retrospectively reviewed. HPD was defined as a more than two- or fourfold increase in tumor growth rate (TGR) or tumor growth kinetics rate (TGK R ) pre- and post-treatment. Overall survival (OS) and baseline characteristics with or without HPD were analyzed. Results A total of 85 patients were included in the analysis. When HPD was defined as a twofold of TGR or TGK R , 8 patients (9.4%, 8/85) had HPD and 11 had PD without HPD. A total of 5 patients (5.9%, 5/85) were diagnosed with HPD and 14 with PD without HPD when HPD was defined as a fourfold of TGR or TGK R . No significant difference was observed in the baseline characteristics and OS between HPD and non-HPD. Conclusion The prevalence of HPD in patients with advanced HCC treated with Atez/Bev was lower than those treated with nivolumab monotherapy. The HPD mechanism in ICI combined with antibodies targeting vascular endothelial growth factor (VEGF) remains to be elucidated.