Angiotensin system inhibitor use is associated with longer survival in resected pancreatic cancer

Abstract

Presenter: Hao Liu MD, PhD | University of Pittsburgh Medical Center Background: The renin-angiotensin system (RAS) has been correlated with pancreatic adenocarcinoma (PDAC) tumorigenesis and progression. Activities and inhibition of RAS may affect the response to systemic therapy and may correlate with clinical outcomes. Previous observational studies suggested that angiotensin system inhibitor (ASI) use is associated with prolonged survival in a subset of PDAC patients. Our present study focused on resected PDAC patients and further explored the protective effect of ASI. Methods: We conducted a single-institution retrospective analysis of resected PDAC patients between 2010-2019. Clinicopathological characteristics of all cases meeting inclusion criteria were reviewed. The effect of ASI on patient survivals was measured by Kaplan Meier analysis, Cox Proportional Hazards model, Propensity Score Matching (PSM), and inverse propensity score weight (IPW) analysis. The propensity score of ASI treatment was calculated, accounting for comorbidities and treatments received, including the use of beta-blockers, diuretics, metformin, and statins. Results: A total of 813 patients were included in the analysis. The average age was 67.0 (34 – 91) years with a median follow up of 20.2 (1.8 – 117.5) months. On average, ASI users were older (69.1 vs. 65.1y, p<0.001) and has higher Charlson comorbidity index (4.6 vs 5.4, p<0.001). However, the use of ASI was significantly associated with longer overall survival in univariate (HR = 0.78 [95%CI: 0.65-0.92], p = 0.004) and multivariate (HR = 0.73 [0.58-0.91], p = 0.005) adjusted analysis. In the propensity score-matched cohort of 637 patients, ASI use confirmed the association with longer overall survival (HR = 0.75 [0.59-0.94], p = 0.013) as well as longer disease-free progression in the liver (HR = 0.66 [0.45-0.95}, p = 0.026) and peritoneum (HR = 0.60 [0.36-0.98] p = 0.041) but not local recurrence-free survival (HR = 0.92 [0.62-1.34], p = 0.653). Lastly, IPW analysis on the whole cohort of 813 patients demonstrated ASI use to be associated with an average treatment effect on the treated (ATT) of HR = 0.67 [0.53-0.85] (p<0.001) for overall survival. Conclusion: In this single institute retrospective study focusing on resected PDAC patients, the use of ASI was associated with longer overall survival after adjusting for multiple clinicopathological parameters. Propensity score matching and inverse propensity score weighted analysis also showed that ASI use was associated with longer overall and progression-free survival. Further prospective trials on the impact of ASI on PDAC are needed.