Chemotherapy-induced neutropenia predicts short-term outcome of patients with pancreatic cancer treated with nanoliposomal irinotecan, fluorouracil, and folinic acid.

Chemotherapy-induced neutropenia has been identified as a potential prognostic marker for multiple cancers. However, only one retrospective study, NN-2301, has investigated the relationship between neutropenia and treatment effects of nanoliposomal irinotecan/5-fluorouracil/folinic acid (NFF) in pancreatic cancer. In this prospective study, we aimed to clarify whether NFF-induced neutropenia could serve as a prognostic marker in pancreatic cancer. Data were analyzed from the prospective cohort of the NAPOLEON-2 trial, an observational study involving patients with unresectable pancreatic cancer treated with NFF. Neutropenia severity was categorized into three cutoffs: Cutoff A (Grade [Gr] 0 vs. Gr 1-4), cutoff B (Gr 0-1 vs. Gr 2-4), and Cutoff C (Gr 0-2 vs. Gr 3-4), using the Common Terminology Criteria for Adverse Events version 5.0, owing to conformity with previous studies and simplicity. The primary endpoint was overall survival (OS); progression-free survival (PFS) was the secondary endpoint. The neutropenic groups included Gr 1, 2, 3, and 4, with 79, 23, 34, and 7 patients, respectively. At each cutoff, OS and PFS were significantly better in the severe neutropenia groups. Higher neutropenia grades correlated with improved OS (log-rank trend test: χ = 8.62, p < .01). Multivariate Cox regression analysis revealed significant differences for all cutoffs: adjusted hazard ratios were 0.57 (95% confidence interval [CI] 0.40-0.83) (Cutoff A), 0.53 (95% CI 0.36-0.78) (Cutoff B), and 0.52 (95% CI 0.34-0.80) (Cutoff C). NFF-induced neutropenia is a valuable prognostic marker in pancreatic cancer and may guide treatment selection.