Prognostic and Predictive Values of Transcriptomic Signatures in Metastatic Pancreatic Cancer: A Biomarker Analysis of Three French Multicenter Prospective Randomized Controlled Phase 2 Trials (Prodige35, Prodige37 and AFUGEM).

Fiche publication

Date publication

juillet 2026

Journal

Cancer letters

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BOUCHE Olivier

Tous les auteurs :
Zhao S, Nicolle R, Taieb J, Dahan L, Abdallah R, Bouché O, Desrame J, Phelip JM, Evesque L, Akouz FK, de Mestier L, Trouilloud I, Malka D, Shen B, Cros J, Laurent-Puig P, Bachet JB

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42521075

Résumé

To evaluate the clinical applicability of previously established transcriptomic signatures (molecular subtypes, components and GemPred status) in metastatic pancreatic cancer, we conducted a retrospective pooled analysis of 178 patients from three phase 2 trials (PRODIGE35/37, AFUGEM; 2013-2016) testing first-line regimens (FOLFIRINOX, GemNab, FuNab, FOLFIRI3). RNA sequencing was performed on primary/metastatic tumors across French centers, with blinded assessment of subtypes (immune classical, pure basal-like, stroma-activated), quantitative components, and GemPred status. Primary endpoint: progression-free survival (PFS). Immune classical subtype showed superior median PFS (9.03 months) and OS (11.27 months) versus basal-like and stroma-activated subtypes (PFS: p=0.015; OS: p=0.010). Higher classical component correlated with improved PFS (HR=0.83, p=0.048) and OS (HR=0.71, p=0.001). Inactive stroma predicted better PFS (HR=0.64, p=0.001) and OS (HR=0.71, p=0.015). GemPred-negative patients treated with FOLFIRINOX versus GemNab had higher ORR (46.9% vs. 19.1%, p=0.046), longer PFS (8.2 vs. 2.3 months; HR=2.28, p=0.008), and OS (11.6 vs. 5.0 months; HR=2.04, p=0.021). No differences occurred in GemPred-positive patients. In a formal treatment-by-GemPred interaction analysis (FOLFIRINOX vs. GemNab), the interaction was significant for OS (adjusted p-interaction=0.050) but not for PFS (adjusted p-interaction=0.51). Transcriptomic signatures retain prognostic and predictive utility in metastatic pancreatic cancer, with GemPred representing a hypothesis-generating predictive signal for OS (e.g., a FOLFIRINOX OS benefit in GemPred-negative). Prospective validation is warranted for clinical implementation.