Abstract B044: Black and Hispanic patients with pancreatic ductal adenocarcinoma (PDAC) have worse overall survival than Asian and White patients with PDAC, despite having more favorable genetic profiles

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer, characterized by late-stage diagnosis, rapid and early metastasis, and high mortality rates. Predisposition to inherited cancer syndromes may increase the likelihood of developing PDAC, and tumor-specific genetics are important in PDAC development, progression, response to treatment, and patient prognosis. Disparities in PDAC patient outcomes based on patient race, ethnicity, and socioeconomic status continue to persist and arise as a combination of genetic factors in the context of differences in access to testing and treatment options among other factors. While disease biology, as a function of genetic ancestry, groups patients by the presence of single-nucleotide polymorphisms arising due to differences in historical individual migration patterns, self-reported race/ethnicity speaks to the interplay between genetics and environment, as self-identity is often associated with lived experiences. Objective: To explore the relationship between self-reported race/ethnicity, recurrent genetic alterations/signatures, and median overall survival. Methods: This is a retrospective study for a cohort of 2164 de-identified patients with stage IV PDAC that received tumor genomic sequencing using the MSK-IMPACT clinical sequencing assay from March 2014 to June 2025. The median overall survival (OS) and genetic mutations for patients that self-reported as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Asian (A), and Hispanic (H) were analyzed using cBioPortal v. 6.3.2. Results: We confirm previous findings that KRAS wildtype (KRAS-WT) PDAC and PDAC with other non-KRAS MAPK pathway alterations (MAPKm) have a better prognosis than KRAS mutant (KRASm) PDAC (Hazard Ratio: MAPKm 0.73, 0.54 - 0.98; KRAS-WT 0.59, 0.40- 0.86). We found that compared to NHW, A present more often with MAPKm tumors, while NHB and H present more often with KRAS-WT tumors. Among patients with KRASm tumors, A are more likely to have non-G12 mutant allele tumors compared to NHW (A 11.2%; NHW 7.7%), while H overall appear to have less Q61 mutant alleles (H <1%; NHW 6.9%). Despite NHB and H presenting more often with KRAS-WT- and MAPKm PDAC that have a better prognosis, NHB and H with PDAC appear to have worse survival outcomes compared to NHW and A (NHB 7.4 months, A 10.6 months, H 9.2 months, NHW 9.4 months, A 10.6 months). Conclusion: Patients with PDAC who self-identify as A, NHB, or H have a younger age at diagnosis than patients that identify as NHW. Moreover, despite enrichment of better prognostic features in PDAC seen in A, H, and NHB (A/H more enriched in MAPKm; NHB more enriched in KRAS-WT), NHB and H with PDAC have worse overall survival. The next step is to investigate alterations in PDAC that are non-KRAS mutant, requiring an increase in the number of tumors sequenced and annotated from patients with PDAC that identify as A, NHB, and H. Citation Format: Jhoely B. Duque-Jimenez, Afua N. Awuah, Amanda Erakky, Subhiksha Nandakumar, Michele Waters, Maria Lao, Karthik Rangavajhula, Anna Varghese, Maria Perry, Amanda Zucker, Christopher Fong, A.Rose Brannon, Diana Mandelker, Nikolaus Schultz, Michael F. Berger, Christine A. Iacobuzio-Donahue, Eileen M. O’Reilly, Debyani Chakravarty, Fiyinfolu Balogun. Black and Hispanic patients with pancreatic ductal adenocarcinoma (PDAC) have worse overall survival than Asian and White patients with PDAC, despite having more favorable genetic profiles [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B044.