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

• Published in: Journal of gastrointestinal oncology Vol. 14; no. 2; pp. 997 - 1007
• Main Authors: Piquemal, David, Bruno, Roman, Bournet, Barbara, Ghiringhelli, Francois, Noguier, Florian, Canivet, Cindy, Bertaut, Aurélie, Pierrat, Fabien, Evesque, Ludovic, Gamez, Amelia, Cros, Jerome, Rederstorff, Emilie, Petit, Erwan, Adnet, Johan, Saint, Angélique, Drouillard, Antoine, Kempf, Emmanuelle, Soularue, Emilie, Vincent, Julie, Baumgaertner, Isabelle, Hennequin, Audrey, Tournigand, Christophe, Trabada Ataz, Daniel Lopez, Bengrine, Leila, Lepage, Come, Manfredi, Sylvain, Afchain, Pauline, Trouilloud, Isabelle, Gagnaire, Alice, LoConte, Noelle K., Bachet, Jean-Baptiste
• Format: Journal Article
• Language: English
• Published: China Baishideng Publishing Group 29.04.2023; AME Publishing Company
• Subjects: Cancer; Life Sciences; Original; gemcitabine-based; predictive diagnosis; Pancreatic cancer; liquid biopsy
• ISSN: 2078-6891; 1948-5204; 2219-679X; 1948-5204
• DOI: 10.21037/jgo-22-946

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. 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 fluoropyrimidine-based regimen. Gemcitabine-based treated patients with a positive GemciTest (22.9%) had a significantly longer progression-free survival (PFS) {5.3 2.8 months; hazard ratio (HR) =0.53 [95% confidence interval (CI): 0.31-0.92]; P=0.023} and overall survival (OS) [10.4 4.8 months; HR =0.49 (95% CI: 0.29-0.85); P=0.0091]. On the contrary, fluoropyrimidine-based treated patients showed no significant difference in PFS and OS using this blood signature. 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.