1558P Pancreatic cancer (PC) in patients (pts) younger than 50 years: Clinical outcomes and actionable genomic/genetic alterations

Limited data has been reported about PC in young pts. Here we describe the epidemiologic, pathologic, and molecular characteristics of the disease in pts ≤ 50 years. VHIO institutional database was queried for medical and treatment history, tumor comprehensive genomics profiling, and germline genetic findings for those pts younger than 50 years old diagnosed with PC between January 2010 and April 2020. Neuroendocrine cancers were excluded. Overall survival (OS) from date of PC diagnosis was estimated using Kaplan-Meier methods. Fisher exact test was used for molecular alterations statistics. In total, 102 pts ≤ 50 years old were identified. Median age at diagnosis was 45 years (55% males). Most pts (54%) were metastatic (M), 19% were locally-advanced (LA) and 27% resectable at diagnosis. First-line treatment (ttm) of choice was FOLFIRINOX in 35 pts (n=14 at LA and n=21 at M stetting) followed by gemcitabine + nab-paclitaxel for 20 pts (n=1 at LA and n=19 at M stetting). Median OS was 19 months (CI95%14-24) in the entire cohort and 42 pts (41%) were included (at least once) in clinical trials. N = 64 underwent successful molecular testing with next generation sequencing and 13/64 (20%) tumors were KRAS wild-type (WT). Young PC pts with KRAS WT PC did not have improved OS as compared to KRAS mutant (mt) population (29.9 vs 20.7 months; p=0.6). Actionable mutations were found in 28% of pts (n=18) with DNA damage repair (DDR) gene mutations accounting for 50% (n=9). Overall, actionable alterations were enriched in KRAS WT as compared to KRAS mt (Odds ratio 6.32; p=0.005), but this association was not significant for germline events (Odds ratio 1.66; p=0.62). In KRAS WT actionable alterations included NRG1 fusions (n=1) and DDR genes mutations in BRCA2 (n=2, both germline), BRCA1 (n=1), PALB2 (n=1) and ATM (n=1). Actionability in KRAS mutant (mt) pts was mostly germline events in DDR genes BRCA2 (n=3, 1 germline). MSH2 (n=1, germline), BRCA1 (n=1, germline). Young PC pts have higher than expected prevalence of KRAS WT tumors (20%) compared to general PC population. KRAS WT PC pts are enriched for somatic actionable alterations compared to KRAS mt population. We advocate for molecular profiling in young-onset PC pts.