Associations of 9p21 deletions on chemotherapy outcomes in pancreatic ductal adenocarcinoma.

783 Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States, with a 5-year survival rate of ~13%. The loss of tumor suppressor CDKN2A/B is well described broadly from molecular profiling of advanced PDAC, representing ~20% of the overall population. Furthermore, the chromosomal loss more broadly at 9p21 can lead to concurrent methylthioadenosine phosphorylase (MTAP) gene loss, for which ongoing strategies are considering the use of PMRT5 inhibitors. Here, we analyze the frequency of 9p21 chromosomal loss in PDAC specifically as stratified by initial clinical presentation and outcomes to first-line chemotherapy between FOLFIRINOX (FFX) and gemcitabine-nab/paclitaxel (G/nPAC). Methods: A retrospective analysis was conducted utilizing PDAC patients (n = 498) from the UW Precision Medicine Molecular Tumor Board. Criteria included histologically confirmed PDAC with available comprehensive genomic profiling. Electronic medical records were queried for baseline demographics and clinical outcomes by treatment regimen. Pathogenic deletions in CDKN2A/B defined 9p21 status. Chi-square testing was used to evaluate variant enrichment in localized versus metastatic disease. Log-rank Kaplan-Meier analysis with censoring was performed to calculate overall survival (OS) defined from initial staging. Results: The population included 52.4% (n=261) with loco-regional disease and 47.6% (n=237) with metastatic disease. Baseline demographics included a median age of 66.5 years and 51.8% female (n=258). 9p21 deletion was seen in 23.5% (n=117) of patients with enrichment in metastatic disease as compared to loco-regional disease (32.1% v. 15.7%, χ 2 =9.68, p