Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.
Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.
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Pancreatic adenocarcinoma (PDAC) remains a refractory disease, however, modern cytotoxic chemotherapeutics can induce tumor regression and extend life. We previously developed a blood-based, pharmacogenomic, ChemoSensitivity Assay using gene expression profiling of circulating tumor and invasive cells (CTICs) to predict treatment response. FOLFIRINOX and gemcitabine/nab-paclitaxel (G/nab-P) are established frontline approaches for treating advanced PDAC, however, there are no validated biomarkers for treatment selection. A similar unmet need exists for choosing second-line therapy. The ChemoSensitivity Assay was evaluated in metastatic PDAC patients presenting for frontline treatment. A prospective study enrolled patients (n=70) prior to receiving either FOLFIRINOX or G/nab-P at a 1:1 ratio. Six mL of peripheral blood was collected at baseline and at time of disease progression. CTICs were isolated, gene-expression profiling was performed and the Assay was used to predict effective and ineffective chemotherapeutic agents. Treating physicians were blinded to the Assay prediction results. Patients receiving an effective regimen as predicted by the ChemoSensitivity Assay experienced significantly longer mPFS (7.8 mo v 4.2 mo, HR = 0.35, p = 0.0002) and mOS (21.0 mo v 9.7 mo, HR = 0.40, p = 0.005), compared with an ineffective regimen. Assay prediction for effective second-line therapy was explored. The entire study cohort experienced favorable outcomes compared with historical controls, 7.1 month median progression-free survival (mPFS) and 12.3 month median overall survival (mOS). ChemoSensitivity Assay profiling is a promising tool for guiding therapy in advanced PDAC. Further prospective validation is underway (ClinicalTrials.gov NCT03033927). We present results from a validation study of an innovative pharmacogenomic tool to predict effective chemotherapeutic drug therapy for patients with advanced pancreatic cancer based on profiling of circulating tumor and invasive cells isolated from peripheral blood. We show that a simple blood test can guide an individualized approach to treating pancreatic cancer, leading to improved survival across the two standard frontline chemotherapy regimens.
