Investigating tumor molecular profiling as a possible contributor to racial/ethnic disparities in pancreatic cancer.

Abstract

6522 Background: A variety of biologic, socioeconomic, and treatment-related factors may contribute to the racial/ethnic disparities observed in pancreatic ductal adenocarcinoma (PDAC) outcomes. As tumor molecular profiling (TMP) is now recommended for patients (pts) with advanced PDAC to inform treatment selection, we hypothesized that rates of TMP, detection of actionable alterations (AA), and use of molecularly-targeted treatments differ across different racial/ethnic groups and may contribute to disparate outcomes. Methods: This retrospective analysis included all Non-Hispanic White (NWH), Asian, Hispanic/Latinx (H/L), and Black/African American (B/AfrAm) pts with PDAC who underwent TMP at UCSF over a 4-yr period. Medical records were reviewed for demographic and disease-specific data. Alterations classified as ‘pathogenic’ or ‘likely pathogenic’ in TMP clinical reports were included, and were categorized as ‘actionable’ if there was clinical or preclinical evidence of benefit from targeted therapy in any cancer. Associations between NHW and other groups were tested with Fishers exact test. Results: Between 1/2016-1/2020, 159/727 (22%) pts underwent PDAC TMP. 60 AA were detected in 54 pts. Rates of TMP or AA detection were not associated with racial/ethnic group (Table). Most AA (33/60, 55%) were associated with the Homologous Recombination DNA Damage Repair (HR-DDR) pathway ( ARID1A n = 15 , ATM n = 7 , and BRCA1 n = 5). Other common AA included PIK3CA alterations (n = 6), CDK4/6 amplifications (n = 5), AKT2 amplifications (n = 4) and KRAS G12C mutation (n = 4). Molecular targets differed between groups (HR-DDR genes comprised 55% AA in NHW vs 100% in H/L, p = 0.03). Regarding treatment, rates of platinum chemotherapy for HR-DDR gene-altered PDAC differed significantly between groups. Three NHW pts with HR-DDR alterations received a PARP-inhibitor +/- ATR inhibitor. Conclusions: To our knowledge, this is the first study to report PDAC TMP rates and therapeutic implications across racial/ethnic groups. Acknowledging the limitations of sample size and what defines AA, we observed no significant differences in rates of testing nor AA detection. Further study is needed to evaluate whether rates of molecularly-informed treatment selection contribute to racial/ethnic disparities in clinical outcomes. As therapeutic advances increase the likelihood of identifying AA, equitable access to both TMP and targeted treatments must be ensured for all pts with PDAC.[Table: see text]