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

Abstract Aim: To clarify the reality of hyperprogressive disease (HPD), a phenomenon with greatly accelerated tumor growth and clinical deterioration rates compared to pre-therapy, 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 (TGKR) 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. At the first imaging, complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were observed in 1 (1.2%), 4 (4.7%), 61 (71.8%), and 19 (22.4%) patients. When HPD was defined as a twofold of TGR or TGKR, 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 TGKR. 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 immune checkpoint inhibitor (ICI) combined with anti-VEGF antibody remains to be elucidated.