Purpose: To broaden access to and implementation of precision medicine in the care of pancreatic cancer patients, the Know Your Tumor (KYT) program was initiated using a turn-key precision medicine system. Patients undergo commercially available multi-omic profiling to determine molecularly rationalized clinical trials and off-label therapies. Experimental Design: Tumor samples were obtained for 640 patients from 287 academic and community practices covering 44 states. CAP/CLIA-accredited laboratories were used for genomic, proteomic and phosphoprotein-based molecular profiling. Results: Tumor samples were adequate for next-generation sequencing in 96% and immunohistochemistry in 91% of patients. A tumor board reviewed the results for every patient and found actionable genomic alterations in 50% of patients (with 27% highly actionable) and actionable proteomic alterations (excluding chemopredictive markers) in 5%. Actionable alterations commonly found were in DNA repair genes (BRCA1/2 or ATM mutations, 8.4%) and cell cycle genes (CCND1/2/3 or CDK4/6 alterations, 8.1%). A subset of samples was assessed for actionable phosphoprotein markers. Among patients with highly actionable biomarkers, those who received matched therapy (n=17) had a significantly longer median progression-free survival (PFS) than those who received unmatched therapy (n=18; PFS = 4.1 vs. 1.9 months; HR: 0.47; 95% CI: 0.24-0.94; adjusted P-value = 0.03). Conclusions: A comprehensive precision medicine system can be implemented in community and academic settings, with highly actionable findings observed in over 25% of pancreatic cancers. Patients whose tumors have highly actionable alterations and receive matched therapy demonstrated significantly increased PFS. Our findings support further prospective evaluation of precision oncology in pancreatic cancer.
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