NAPAN Trial in Metastatic Pancreatic Cancer: EJC/ March 2026

Introduction:

Metastatic pancreatic cancer continues to carry a dismal prognosis, with limited effective options after failure of first-line gemcitabine-based therapy. Liposomal irinotecan (nal-IRI) combined with 5-fluorouracil/leucovorin (5-FU/LV) is currently an established second-line standard. However, S-1, an oral fluoropyrimidine widely used in Asian populations, has shown promising efficacy and convenience, raising the possibility of an alternative combination strategy with nal-IRI.

Problem Statement and Summary:

The NAPAN trial was designed to evaluate whether nal-IRI plus S-1 could outperform the current standard nal-IRI plus 5-FU/LV in second-line treatment. However, the study failed to demonstrate superiority, with shorter progression-free survival and a trend toward inferior overall survival in the S-1 arm. While toxicity profiles were comparable, no clinical advantage was observed with S-1. These findings reinforce nal-IRI plus 5-FU/LV as the standard second-line regimen and highlight the ongoing challenge of improving outcomes in metastatic pancreatic cancer beyond current chemotherapy backbones.