Mutated KRASas a promising target in pancreas cancer: PURPLE registry data to inform real-world incidence and prognostic significance and to aid trial recruitment.

11150 Background: With around 90% KRASmutation (mt) frequency, pancreatic ductal adenocarcinoma (PDAC) is considered the most RAS-addicted cancer. Despite guideline recommendations, genomic testing is not routine in all PDAC patients (pts) in Australia, due to unproven clinical impact. As more novel KRAS-direct therapeutics enter clinical trials, understanding the real-world frequency of individual mutations and prognostic significance, and facilitating trial recruitment are important goals, all of which can be supported by registry data. Methods: Data extracted from the PURPLE pancreatic cancer registry from 9 participating Australian cancer centres, between 2016-2022, was analysed to compare clinicopathological features, survival based on KRASmt status, and assess feasibility of the platform to identify and molecularly stratify patients for future clinical trials. Survival estimates were calculated using Kaplan-Meier curves and log-rank testing on SPSS (Macintosh v.29). Results: Of 721 PDAC routine care pts identified, next generation sequencing (NGS) was undertaken in 378/721 (52%). Median patient age was 68 years (range 52-83); 152 (40%) had resectable, 111 (29%) locally advanced and 115 (30%) metastatic disease. 57/378 (15%) were KRAS wildtype. Of 321 pts with a KRAS mt, codons 12,13, and 61 were the most common sites of mt, including G12D (45%), and G12V (30%), with lower frequencies of G12R (13%), Q61H (6%), G12A (3%), G12C (1%), and G13D (1%). Comparing KRAS wildtype to KRASmt pts, there was no difference in median age (68 vs 67, p=0.63), gender (male: 49% vs 60%, p=0.23), Charlson comorbidity index (p=0.30), or stage at first presentation (p=0.99). Overall KRAS wildtype pts were more likely to be ECOG PS 0 at diagnosis (p=0.01) and to receive at least 1 modality of treatment (p=0.004). For all pts, median overall survival (OS) in KRASwildtype versus KRAS mt pts was 29.0 months versus 19.7 months (p=0.007), and for the 115 metastatic pts 15.1 versus 10.4 months (p=0.28). Further analysis of the impact by disease stage and by individual RAS mt is underway. Conclusions: Registry based analysis informs understanding of KRAS mt status of PDAC in a community setting. Here, KRAS mt status was associated with worse OS outcomes, likely in part due to the association with ECOG PS and receiving less active treatment. With newer promising KRAS-targeted therapies becoming available in clinical trials, known RAS status will aid identification of trial candidates. The clinical utility of NGS and rationale for reflex testing in PDAC is increasing. Clinical Registry information (ACTRN12617001474347).