Outcomes of beta blockers (BB) in hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs).

399 Background: Portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, leading to a pro-inflammatory state, which can in turn promote progression of liver disease. However, multiple studies have shown that BB use in patients with cirrhosis can reduce the risk of developing HCC, and in patients with HCC, BB can improve overall survival (OS). In recent years, ICIs have become first-line therapy for patients with unresectable HCC, and we aimed to evaluate whether BB use conferred survival benefits in patients treated with ICIs using real-world data. Methods: We conducted a retrospective chart review of HCC patients treated with ICI from 2017 to 2019 at 13 institutions across North America, Europe, and Asia in order to evaluate the association between BB use and OS, as well as BB use and overall response rate (ORR). Univariable and multivariable logistic regression models were used to evaluate associations, and survival analyses were performed using the Kaplan-Meier method. Results: A total of 578 patients were evaluated. The median age of the cohort was 65 years, and 80% of patients were male. The majority of patients (70%) were cirrhotic. The causes of underlying liver disease were as follows: HBV (22%), HCV (36%), alcohol (20.8%), and NASH (13%). Most patients (73.5%) had Child Pugh (CP) class A liver disease, and good performance status with ECOG score either 0 (52%) or 1 (45%). The majority of patients (75%) treated with ICIs received a PD-1 inhibitor alone. There were 360 deaths (62% of patients) with a median follow-up of 30.8 months (Quartiles: 17.2-40.3 months). Two hundred and three (35%) patients had BB use at any point during ICI therapy. Fifty-one percent of these patients were on a nonselective BB whereas 49% were taking a cardio-selective BB. BB use was not significantly correlated with OS (hazard ratio, 1.12; 95% CI, 0.9-1.39; P = 0.298) or ORR (odds ratio, 0.84; 95% CI, 0.54-1.31; P = 0.451) in univariate or multivariate analyses. Conclusions: Patients who used BB while on immunotherapy for unresectable HCC did not have statistically significant differences in OS or ORR compared to patients who did not use BB. More studies are required to elucidate the effect of beta blockade on the microbiome, immune activation, and HCC.