Molecular profiling of patients with pancreatic cancer: Initial results from the know your tumor initiative

Michael J. Pishvaian, Robert J. Bender, David Halverson, Lola Rahib, Andrew E. Hendifar, Sameh Mikhail, Vincent Chung, Vincent J. Picozzi, Davendra Sohal, Edik M. Blais, Kimberly Mason, Emily E. Lyons, Lynn M. Matrisian, Jonathan R. Brody, Subha Madhavan, Emanuel F. Petricoin

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Purpose: To broaden access to and implementation of precision medicine in the care of patients with pancreatic cancer, the Know Your Tumor (KYT) program was initiated using a turn-key precision medicine system. Patients undergo commercially available multiomic 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. College of American Pathologists/Clinical Laboratory Improvement Amendments-accredited laboratories were used for genomic, proteomic, and phosphoproteinbased molecular profiling. Results: Tumor samples were adequate for next-generation sequencing in96%and IHC in91%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% confidence interval (CI): 0.24-0.94; Padj = 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.

Original languageEnglish (US)
Pages (from-to)5018-5027
Number of pages10
JournalClinical Cancer Research
Volume24
Issue number20
DOIs
StatePublished - Oct 15 2018
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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