Visualizing real-world outcomes through the lens of a molecular tumor board: Persona-typing pancreatic cancers for clinical decision support.

person Emanuel Petricoin George Mason University, Manassas, VA info_outline Emanuel Petricoin, Daniel Barg, Patricia Miren de Arbeloa, Michael J. Pishvaian, Edik Matthew Blais

Authors person Emanuel Petricoin George Mason University, Manassas, VA info_outline Emanuel Petricoin, Daniel Barg, Patricia Miren de Arbeloa, Michael J. Pishvaian, Edik Matthew Blais Organizations George Mason University, Manassas, VA, Perthera, Mclean, VA, Georgetown University Medical Center, Washington, DC, Perthera, Inc., Mclean, VA Abstract Disclosures Research Funding Other Other Foundation, Pancreatic Cancer Action Network Background: Despite the molecular diversity of pancreatic adenocarcinoma, standard therapy options remain largely molecularly-untailored except in the context of DNA damage response alterations such as BRCA mutations, NTRK fusions, or microsatellite instability. Methods: To broaden the utility of molecular profiling, we analyzed real-world outcomes and established 12 molecularly-driven clusters, or “persona types” (PTs), across a cohort of 1280 pancreatic cancers with CLIA-grade genomic/proteomic data (commercially available NGS/IHC panels). Patients were consented into Perthera’s precision oncology platform via referrals from advocacy programs and hospital partnerships for case review by a molecular tumor board (MTB). Persona types were generated using unsupervised k-means clustering of molecularly-tailored therapy recommendations formulated by the MTB. Progression-free survival was documented across all lines of therapy. Results: Personas based on multi-omic profiles and expert-driven recommendations were representative of molecular phenotypes reported in previous studies (e.g. DNA damage response deficiencies, BRAF mutations, other non-KRAS-drivers, SWI/SNF alterations, squamous-associated genes, cell cycle regulators, etc.). To streamline the exploration of real-world outcomes, we developed an interactive dashboard that enables users to compare PFS survival curves across Personas for various therapies such as gemcitabine/nab-paclitaxel, FOLFIRINOX, other standard regimens, immunotherapy, PARP inhibitors, RAF/MEK/ERK inhibitors, and more. Persona types associated with increased/decreased sensitivity to several classes of agents were identified (e.g. PD-1/L1 inhibitors in a persona enriched for cell cycle dysregulation, PARP inhibitors in a persona enriched for BRCA mutations). Conclusions: Empowering oncologists with personalized insights into real-world outcomes may promote investigator-initiated trials and augment clinical decision support, particularly when choosing between standard of care regimens or when exploring potential clinical trial options.