1667P Clinical and molecular features of young onset pancreatic adenocarcinoma

Pancreatic adenocarcinoma (PDAC) has a poor prognosis and a growing incidence, especially in patients (pts) ≤ 50 years (e.g., young onset YoPA). We aim to describe clinical and molecular features (genomic and transcriptomic) of YoPA. A retrospective chart review (demographics, systemic therapies, and outcomes) was performed in consecutive PDAC pts followed in our institution between 2012-2022. Tumor molecular profiling was performed as part of MATCH-R (NCT02517892) or STING (NCT04932525) trial (mostly Foundation Medicine® on tumor tissue (56.4%) or liquid biopsy (43.6%)). RNA sequencing was performed as part of MATCH-R trial. Overall, 878 pts were included, of them 113 were YoPA, with similar performance status at diagnosis. YoPA were more often diagnosed at metastatic (met) stage (69.7% vs 58.3%, p=0.024). In particular, hepatic mets were more present at diagnosis in YoPA (60.2% vs 43.9%, p=0.002). Conversely, lung and bone mets tended to be less frequent in YoPA. Location of the primary tumor (head vs tail) was not different between groups. Regarding treatment outcomes, among the 239 pts with resectable or borderline disease, 217 (91%) underwent surgery (22 YoPA and 195 nYoPA). The median recurrence-free survival (RFS) was 12.0 months (mos) (95CI: 10.6-14.8) (similar between YoPA and nYoPA). Among the 746 pts with mets, 96% received at least 1 line of systemic therapy. YoPA received more lines (41.6% vs 31.0% received ≥ 3 lines, p = 0.045). 1st line PFS was not different between groups. The median overall survival (OS) was 18.2 mos, with no difference between YoPA and nYoPA (HR=1.01, 95%CI= 0.81-1.26). In mets, OS was 12.8 mos (95%CI: 11.8-14.0) and was similar between groups. 312 pts had molecular profile including 49 YoPA. Mean TMB was lower in YoPA (1.42 vs 2.95 mut/Mb, p<0.002). YoPA and nYoPAs had similar prevalence of mutations in KRAS (88%) and BRCA1/2 (6.3%). Conversely, YoPA displayed fewer alterations in CNKN2A/B (p=0.03). RNA sequencing data is available for 84 pts and the analysis is in progress. YoPA were more often diagnosed at the metastatic stage with a higher prevalence of hepatic mets and had similar OS to nYoPA. They displayed a different molecular profile with lower TMB and fewer alterations in CDKN2A/B.