Using next-generation sequencing to determine potential molecularly guided therapy options for patients with resectable pancreatic adenocarcinoma

Abstract

BackgroundGenomic sequencing technology may identify personalized treatment options for patients with pancreatic adenocarcinoma. MethodsThe study was conducted using tissue specimens obtained from 2012 to 2014. Patients with resected pancreatic adenocarcinoma were identified. Next-generation sequencing was performed from paraffin-tumor blocks. Mutational profiles were reviewed to determine available targeted therapies and clinical trial eligibility. ResultsThirty patients were identified. The incidence of mutations was: Kirsten rat sarcoma viral oncogene homolong (KRAS) = 87%, tumor protein 53 (TP53) = 63%, cyclin-dependent kinase inhibitor 2A (CDKN2A) = 20%, Mothers Against Decapentaplegic Homolog 4 (SMAD4) = 20%, epidermal growth factor receptor (EGFR) = 7%. Multiple mutations were found in 73%. All CDKN2A mutations occurred in male patients (P = .06), and there was a trend toward younger patient age in this group (P = .13). Potential for Federal Drug Administration (FDA)-approved targeted therapies was identified in 8 of 30 (27%). In addition, 29 of 30 (97%) had mutations applicable for ongoing phase I or II clinical trials. ConclusionsNext-generation sequencing of resected pancreatic adenocarcinoma specimens can determine common genetic mutations and identify patients who may be eligible for off-label use of targeted therapies or clinical trial enrollment.