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.

High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma

“… [1] , [2] , [3] Although people who respond to this combination therapy have favourable clinical outcomes, a fraction of these still exhibit intrinsic resistance. [4] , [5] , [6] , [7] This limitation could be overcome by optimising atezolizumab and bevacizumab (Ate/Bev) therapy using an optimal biomarker that can precisely predict clinical responses or intrinsic resistance before treatment initiation. However, the development of predictive biomarkers through tumour tissue analysis is limited in HCC relative to other solid cancers, because tissue biopsy is not mandatory for diagnosing HCC and can be limited by tumour inaccessibility and the person’s medical condition.…”