lunes, 9 de julio de 2018

Molecular Profiling of Pancreatic Cancer Patients: Initial Results from the Know Your Tumor Initiative. - PubMed - NCBI

2018 Jun 28. pii: clincanres.0531.2018. doi: 10.1158/1078-0432.CCR-18-0531. [Epub ahead of print]

Molecular Profiling of Pancreatic Cancer Patients: Initial Results from the Know Your Tumor Initiative.

Pishvaian MJ1, Bender RJ2, Halverson D3, Rahib L4, Hendifar AE5, Mikhail S6, Chung V7, Picozzi VJ8, Sohal D9, Blais EM2, Mason K2, Lyons EE4, Matrisian LM4, Brody JR10, Madhavan S11, Petricoin EF12.

Author information

Abstract

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.