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. 2023 Apr 29;14(2):997-1007.
doi: 10.21037/jgo-22-946. Epub 2023 Apr 10.

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

David Piquemal  1 , Roman Bruno  1 , Barbara Bournet  2 , Francois Ghiringhelli  3 , Florian Noguier  1 , Cindy Canivet  2 , Aurélie Bertaut  3 , Fabien Pierrat  1 , Ludovic Evesque  4 , Amelia Gamez  1 , Jerome Cros  5 , Emilie Rederstorff  3 , Erwan Petit  3 , Johan Adnet  3 , Angélique Saint  4 , Antoine Drouillard  6 , Emmanuelle Kempf  7 , Emilie Soularue  8 , Julie Vincent  3 , Isabelle Baumgaertner  7 , Audrey Hennequin  3 , Christophe Tournigand  7 , Daniel Lopez Trabada Ataz  8 , Leila Bengrine  3 , Come Lepage  6 , Sylvain Manfredi  6 , Pauline Afchain  8 , Isabelle Trouilloud  9 , Alice Gagnaire  6 , Noelle K LoConte  10 , Jean-Baptiste Bachet  11
Affiliations

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

David Piquemal et al. J Gastrointest Oncol. .

Abstract

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 fluoropyrimidine-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; hazard ratio (HR) =0.53 [95% confidence interval (CI): 0.31-0.92]; P=0.023} and overall survival (OS) [10.4 vs. 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.

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.

Keywords: Pancreatic cancer; gemcitabine-based; liquid biopsy; predictive diagnosis.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-946/coif). DP, RB, FN, FP and A Gamez report that they are employed by Acobiom company. JBB reports that he received personal fees from Acobiom, Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier, Viatris, and non-financial support from Amgen, Merck Serono, and Roche. NKL reports that she is advisory board member for Abbvie and PDGX). The other authors have no conflicts of to declare.

Figures

Figure 1
Figure 1
Diagram of the selection and categorization of patient populations, and treatment regimens. *, a patient could meet different categories. EU, Europe Centres; FR, French Centres; US, US Centres; UWCCC, University of Wisconsin Comprehensive Cancer Center; TSB, Translational Science Biocore; BACAP, BAse Clinico-biologique sur l’Adénocarcinome du Pancréas; IVD, In Vitro Diagnostic; qPCR, quantitative polymerase chain reaction; 5FU, 5-fluorouracil.
Figure 2
Figure 2
Kaplan-Meier plots for PDAC patients gemcitabine-based and 5FU-based regimens. Kaplan-Meier plots for both PFS and OS. The red curve identifies the gem-based patients. The black curve identifies the 5FU-based patients. The x-axis represents the number of days. PFS, progression free survival; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma; 5FU, 5-fluorouracil.
Figure 3
Figure 3
Kaplan-Meier plots for patients who received either a gemcitabine- or fluoropyrimidine-based regimen according to the GemciTest classification. Kaplan-Meier for both PFS and OS for mPDAC patients (A,B) treated with gem-based regimen, for LAPC patients (C,D) treated with gem-based regimen, and for mPDAC patients (E,F) treated with 5FU-based regimen. The red curve identifies patients positive to the GemciTest, and the black curve patients negative to the GemciTest. The x-axis represents the number of days. PFS, progression-free survival; OS, overall survival; mPDAC, metastatic pancreatic ductal adenocarcinoma; LAPC, locally advanced PDAC; 5FU, 5-fluorouracil.
Figure 4
Figure 4
Kaplan-Meier plots for mPDAC patients with a positive GemciTest and treated with a gemcitabine-based regimen, versus whole patients treated with a 5FU-based regimen without molecular profiling. Kaplan-Meier plots for both PFS and OS. The red curve identifies the patient whose blood-based transcriptomic profile is favorable to gemcitabine-based treatment as a first-line therapy. The black curve identifies the patient with 5FU-based regimen as a first-line therapy. The x-axis represents the number of days. PFS, progression-free survival; OS, overall survival; 5FU, 5-fluorouracil; mPDAC, metastatic pancreatic ductal adenocarcinoma.
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