Predictors of prolonged progression-free survival in patients with unresectable or recurrent pancreatic cancer treated with nanoliposomal irinotecan with fluorouracil and folinic acid (NAPOLEON-2 study).

Abstract

Background: Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second- or later-line regimen for unresectable or recurrent pancreatic cancer (urPC). However, validated prognostic biomarkers are lacking.

Objectives: In this study, we aimed to identify clinical predictors of progression-free survival (PFS) in patients receiving NFF and to develop a nomogram for early prediction of therapeutic efficacy.

Design: This was a pre-planned analysis of a prospective, multicenter observational study conducted across 17 hospitals in Japan.

Methods: We enrolled 150 patients with urPC who received NFF between 2021 and 2023. Prognostic factors independently associated with PFS were identified using multivariable Cox proportional hazards regression analysis. Based on these factors, we constructed a nomogram to estimate the probabilities of 2-, 4-, and 6-month PFS. Finally, we performed risk stratification according to total nomogram scores and validated this model using an independent retrospective cohort.

Results: The median overall survival was 7.8 months, and the median PFS was 3.7 months. Multivariable analysis identified a longer duration of previous chemotherapy (hazard ratio (HR), 0.52; 95% confidence interval (CI), 0.38-0.71; p < 0.01) as a favorable prognostic factor; third-line treatment (vs second-line; HR, 1.67; 95% CI, 1.04-2.67, p = 0.03) and higher C-reactive protein/albumin ratio (CAR; HR, 1.14; 95% CI, 1.01-1.29, p = 0.04) were associated with unfavorable PFS. In risk stratification, median PFS in the low-, moderate-, and high-risk groups was 5.9 months (reference), 3.9 months (HR, 1.78; 95% CI, 1.16-2.71; p < 0.01), and 2.2 months (HR, 2.30; 95% CI, 1.51-3.50; p < 0.01), respectively. Significant risk stratification was also confirmed in an independent retrospective cohort.

Conclusion: The duration of previous chemotherapy, treatment line, and the CAR are useful predictors of PFS in patients with urPC receiving NFF. The proposed nomogram and risk stratification system may facilitate individualized treatment planning and support clinical decision-making.