Clinical and molecular presentation of KRAS G12D-mutated pancreatic ductal adenocarcinoma in real-world settings.

• DOI: 10.1200/jco.2023.41.4_suppl.738
• Publication Date: 2023-01-24T21:05:07Z
• Authors: Emma G. Sturgill; Sahiti Kolli; Kavanya Feustel; Daniel Luckett; Carissa Jones; Marilyn Elaine Holt; Annastasia Hyde; Suzanne Fields Jones; Cesar Augusto Perez; Judy S. Wang; Stephen G. Divers; Meredith Pelster; Jason Timothy Henry; David R. Spigel; Howard A. Burris III; Andrew Jacob McKe...
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

738 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating diagnosis with an overall 5-year survival rate of ~10%. Therapies targeting KRAS G12D, prevalent molecular driver PDAC, represent active area investigation many agents currently in clinical development. This study characterizes the real-world clinico-genomic landscape patients G12D-mutated PDAC to inform ongoing therapeutic development and trial design. Methods: We conducted retrospective, records-based analysis 2,805 from across 299 community-based oncology clinics. All had broad-panel next generation sequencing (NGS) commercial vendors performed as standard care. Patients were stratified into WT (26%), G12D (31%), non-G12D (43%) cohorts according NGS results assessed for co-mutations, survival, time chemotherapy failure. Results: The exhibited similar mutational landscapes frequent alterations TP53, CDKN2A, SMAD4 ( > 20% frequency occurrence) infrequent actionable co-mutations (i.e. ATM, MTAP, BRCA1/2, PIK3CA, MYC; < 5% occurrence). significantly decreased compared (m (95% CI); 32.4 months (27.6-37.6 months) [ ], 20.1 (17.0-22.7 21.7 (20.0-25.0 ]; Cox model p-value 0.001) well shortened failure both 10.8 (9.6-11.6 7.8 (7.3-8.7 9.8 (8.8-11.1 0.01). Within cohort, no associated survival. Conclusions: demonstrates acute need G12D-targeted clinic, G12D-driven experience particularly poor patient outcomes lack alternative targets.