Comparative outcomes of first-line atezolizumab plus bevacizumab (A+B) and durvalumab plus tremelimumab (D+T) in hepatocellular carcinoma (HCC).

4163 Background: Standard first-line systemic therapy for hepatocellular carcinoma involves immune checkpoint inhibitors, including A+B and the STRIDE regimen consisting of D+T. However, there is limited data comparing outcomes of patients receiving these two regimens. We aimed to compare the survival and safety profiles of patients receiving A+B versus D+T as first-line systemic therapy for advanced HCC in a propensity score matched analysis. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. We identified adult patients with a history of HCC and included those who received A+B or D+T as first line treatment. Propensity score matching (PSM) was conducted, matching for patient demographics (age, sex, race), clinical history (alcohol use, ascites, esophageal varices, viral hepatitis), and laboratory parameters [platelets, albumin, bilirubin, INR, alpha-1-fetoprotein (AFP)]. Median overall survival (mOS) and relevant patient safety events were compared between those who received A+B or D+T. Results: We identified 2,762 patients who had HCC who were treated with A+B or D+T, of which 2,030 patients received A+B and 723 patients received D+T. Compared to patients in the A+B cohort, those who received D+T were more often older (68.5 vs 66.9 years, standardized mean difference (SMD) = 0.17), had lower platelet counts (186.4 vs 198.6, SMD = 0.11), had higher prevalence of ascites (33.1% vs 20.3%, SMD = 0.29), and alcohol use (23.8% vs 18.8%, SMD = 0.12). After PSM, 723 patients were included in survival analyses, with all variables adequately balanced except for albumin, which was higher in the A+B group (3.6 vs 3.5, SMD = 0.19). At 90 days after starting therapy, D+T was associated with higher incidence of immune-mediated colitis [5.3% vs 2.6%, odds ratio (OR) 2.1; 95% confidence interval (CI), 1.2-3.7], and a higher risk of hospitalization [35.4% vs 27.9%, OR 1.4; 95% CI, 1.1-1.8]. At 6 months, the risk of hypertension and proteinuria was higher in the A+B cohort [21.9% vs 13.7%, OR 0.57; 95% CI, 0.34-0.95], which persisted at 1 year [28.1% vs 16.5%, OR 0.51; 95% CI, 0.32-0.81]. There was no significant difference in mOS between those receiving A+B or D+T [18.3 months vs 22.8 months, hazard ratio (HR) 0.94; 95% CI, 0.79-1.1]. Conclusions: In patients with advanced HCC who received A+B or D+T as first-line systemic therapy, we found that A+B was associated with higher risk of hypertension and proteinuria, while D+T was associated with a higher risk of immune-mediated colitis and hospitalization. No significant difference in mOS was observed between the cohorts. These findings suggest that safety profiles, rather than survival differences, may be used to guide optimal first-line treatment regimens. Prospective studies are warranted to further assess differences in patient outcomes.