Using Exome Sequencing to Improve Prediction of FOLFIRINOX First Efficacy for Pancreatic Adenocarcinoma
Purpose: The first line treatment of advanced pancreatic ductal adenocarcinoma cancer (PDAC) comprises a FOLFIRINOX regimen for most patients with good performance status. However, no biomarker to predict efficacy is currently available. We investigated whether exome sequencing could be used to predict progression-free and overall survival in patients undergoing FOLFIRINOX for PDAC. Methods: In this single-center observational study, we included 78 patients with advanced PDAC who underwent somatic and germline exome analyses during first line therapy with FOLFIRINOX or gemcitabine. Exome-derived variables associated with outcome were then used in Cox regression models to generate a composite biomarker. Results: Performance status, tumor stage, liver metastasis, and lung metastasis were retained to generate a prognostic clinical score associated with overall and progression-free survival. Clonality, ploidy, and copy number variant (CNV) signatures 1 and 5, as well as gene variants in the calcium, non-homologous end-joining (NHEJ), and spliceosome pathways, were retained to generate a genomic prognostic score. The addition of genomic score improved the prediction of prognosis compared to the clinical score alone. Conclusions: This study underlines that structural and pathway genomic features could be used to predict FOLFIRINOX survival in patients with advanced PDAC.