Performance of a blood-based RNA signature for gemcitabine-based treatment in metastatic pancreatic adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, and chemotherapy is a key treatment for advanced PDAC. Gemcitabine chemotherapy is still an important component of treatment; however, there is no routine biomarker to predict its efficacy. Predictive tests may help clinicians to decide on the best first-line chemotherapy. Methods: This study is a confirmatory study of a blood-based RNA signature, called the GemciTest. This test measures the expression levels of nine genes using real-time polymerase chain reaction (PCR) processes. Clinical validation was carried out, through a discovery and a validation phases, on 336 patients (mean 68.7 years; range, 37-88 years) for whom blood was collected from two prospective cohorts and two tumor biobanks. These cohorts included previously untreated advanced PDAC patients who received either a gemcitabine- or f luoropyrimidine-based regimen. Results: Gemcitabine-based treated patients with a positive GemciTest (22.9%) had a significantly longer progression-free survival (PFS) [5.3 vs. 2.8 months; HR =0.53 (95% CI: 0.31-0.92); P=0.023] and OS [10.4 vs. 4.8 months; HR =0.49 (95% CI: 0.29-0.85); P=0.0091]. On the contrary, f luoropyrimidine-based treated patients showed no significant difference in PFS and OS using this blood signature. Conclusions: The GemciTest demonstrated that a blood-based RNA signature has the potential to aid in personalized therapy for PDAC, leading to better survival rates for patients receiving a gemcitabine-based first-line treatment.