Factors associated with actionable gene aberrations in pancreatic cancer based on the C-CAT database

J Gastroenterol. 2025 May 2. doi: 10.1007/s00535-025-02253-9. Online ahead of print.

ABSTRACT

BACKGROUND: Comprehensive genomic profiling (CGP) tests are increasingly used to explore the genomically matched therapies for solid tumors. The aim of this study is to investigate factors associated with actionable gene aberrations in pancreatic cancer (PC) using real-world data from the Center for Advanced Cancer Genome Therapy (C-CAT) database.

METHODS: Among 6768 patients with unresectable and recurrent PC registered in the C-CAT database between June 2019 and July 2023, we identified 4628 patients who underwent tissue-based CGP tests using either FoundationOne^® CDx (F1CDx) or OncoGuide^™ NCC Oncopanel (NOP). We investigated the incidence of actionable gene aberrations and the factors associated with their detection.

RESULTS: The cohort included 3,554 patients who underwent F1CDx and 1128 NOP, with surgical specimens in 50% of the cases. Adenocarcinoma was the predominant subtype (95%), and KRAS mutations were found in 90%. The overall incidence of actionable gene aberrations was 27%. The most common gene abnormalities were BRCA2 (3.4%), followed by ATM (2.9%), ERBB2 (2.8%), PIK3 CA (2.5%), and BRAF (1.9%). Multivariable analysis revealed that acinar cell carcinoma (ACC) (Odds ratio [OR] 1.87, 95% confidence interval [CI] 1.00-2.67), KRAS wild type (KRAS_WT) (OR 3.09, 95% CI 2.49-3.85), and use of F1CDx (OR 2.38, 95% CI 1.98-2.85) were significantly associated with actionable gene aberrations.

CONCLUSIONS: Actionable gene aberrations were more likely in cases of ACC, KRAS_WT, and F1CDx usage. The choice of CGP test should be made on a case-by-case basis, as other factors beyond actionable gene aberrations also need to be considered.

PMID:40314773 | DOI:10.1007/s00535-025-02253-9