Glycemic control determines the response to immunotherapy for hepatocellular carcinoma in subjects with diabetes

Aims: Although diabetes is highly correlated with hepatocellular carcinoma (HCC), it remains unclear how glycemic status affects responses to immunotherapy for HCC. Therefore, this study aimed to determine the prognostic implications of glycemic status and its impacts on immunotherapy treatment in HCC. Methods: This retrospective study included 151 subjects with HCC who were treated with atezolizumab and bevacizumab. Subjects were categorized into three groups, including non-diabetes group (N=83), well-controlled diabetes group (HbA1c<7.0%; N=37), and poorly-controlled diabetes group (HbA1c≥7.0%; N=31). Therapeutic response was evaluated using modified response evaluation criteria in solid tumors. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method. Prognostic factors were analyzed with Cox proportional hazards models. Results: The poorly-controlled diabetes group exhibited the worst therapeutic response and significantly unfavorable PFS and OS, as compared with well-controlled diabetes and non-diabetes groups. Subgroup analysis showed that PFS and OS for well-controlled diabetes group were comparable to non-diabetes group. Furthermore, the poorly-controlled diabetes was an independent predictor of reduced PFS (HR=3.52, 95% CI:1.98-6.24, P<0.001) and OS (HR=5.16, 95% CI:2.38-11.18, P<0.001). Conclusions: Our findings show that poor glycemic control in subjects with diabetes predicts worse survival and immunotherapy treatment response to HCC.