Predictive Values of Blood-Based RNA Signatures for the Gemcitabine Response in Advanced Pancreatic Cancer

Simple Summary Pancreatic adenocarcinoma is predicted to be the 2nd cause of death by cancer in Western Countries in 2023. Most patients are diagnosed at an advanced stage for which chemotherapy is the main treatment. In this study we developed through an innovative approach, a simple nine genes blood RNA-based signature that predicts sensitivity to gemcitabine, one of the main regimens in combination with nab-paclitaxel or alone in less fit patients. Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second cause of cancer death by 2022. For nearly 80% of patients, diagnosis occurs at an advanced, nonsurgical stage, making such patients incurable. Gemcitabine is still an important component in PDAC treatment and is most often used as a backbone to test new targeted therapies and there is, to date, no routine biomarker to predict its efficacy. Samples from a phase III randomized trial were used to develop through a large approach based on blood-based liquid biopsy, transcriptome profiling, and machine learning, a nine gene predictive signature for gemcitabine sensitivity. Patients with a positive test (41.6%) had a significantly longer progression free survival (PFS) (3.8 months vs. 1.9 months p = 0.03) and a longer overall survival (OS) (14.5 months vs. 5.1, p < 0.0001). In multivariate analyses, this signature was independently associated with PFS (HR = 0.5 (0.28-0.9) p = 0.025) and OS (HR = 0.39 (0.21-0.7) p = 0.002).