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Prognostic and predictive values of transcriptomic signatures in metastatic pancreatic cancer: A biomarker analysis
Shulin Zhao1, Remy Nicolle2, Julien Taieb3
1Centre de Recherche des Cordeliers, INSERM UMRS1138, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe Labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Research Institute of Pancreatic Disease, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of General Surgery, Ruijin-Hainan Hospital, Shanghai Jiao Tong University School of Medicine (Hainan Boao Research Hospital), Qionghai, China.
None:
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 OS (HR = 0.737, p = 0.005) but not PFS (HR = 0.90, p = 0.339). Inactive stroma predicted better PFS (HR = 0.66, p = 0.003) and OS (HR = 0.697, p = 0.013). 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.
