Purpose: FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) are the most commonly administered first-line (1L) regimens for advanced, nonresectable, pancreatic ductal adenocarcinoma (PDAC). In the absence of biomarkers to predict response, clinical covariates such as age and performance status are often used by clinicians to select optimal treatment regimens. Purity independent subtyping of tumors (PurIST) is a molecular subtyping algorithm that classifies tumors as classical or basal. The current study was designed to validate PurIST as a prognostic biomarker for patients receiving 1L FFX and as a predictive biomarker for patients more likely to benefit from FFX versus GnP.
Patients and methods: This is a prospectively designed, retrospective study using a real-world data set of 931 patients with advanced PDAC, treated with either 1L FFX or GnP, and designed to demonstrate associations of PurIST subtypes with clinical outcomes. The primary end point was overall survival (OS) in classical versus basal patients treated with 1L FFX, while the secondary end point was OS in classical patients-with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1-to compare 1L FFX versus GnP.
Results: Within the cohort of patients receiving 1L FFX (n = 536), basal subtype patients had a median OS of 7 months compared with classical subtype patients with a median OS of 11.8 months (hazard ratio [HR], 1.86 [95% CI, 1.49 to 2.33]; P < .001). In an analysis restricted to patients with classical subtype and ECOG PS of 0 or 1 (n = 311), there was a 33% relative risk reduction of death in patients treated with FFX compared with GnP, adjusting for age and ECOG PS (HR, 0.67 [95% CI, 0.48 to 0.94]; P < .009), with no comparable risk reduction in basal patients (subtype-treatment interaction, P = .002).
Conclusion: Patients with PDAC of the PurIST classical subtype showed a significant OS benefit when treated with FFX as 1L versus GnP.