NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors

Eur J Cancer. 2019 Feb;108:78-87. doi: 10.1016/j.ejca.2018.12.007. Epub 2019 Jan 14.


Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial.

Patients and methods: Patients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) for the first 4 weeks of 6-week cycles. Baseline characteristics and efficacy in the overall population were compared with those in patients who survived ≥1 year. Through 16th November 2015, 382 overall survival events had occurred.

Results: The overall survival advantage for nal-IRI+5-FU/LV vs 5-FU/LV was maintained from the original nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1) analysis (6.2 vs 4.2 months, respectively; HR, 0.75; 95% confidence interval: 0.57-0.99). Median progression-free survival, objective response rate and disease control rate also favoured nal-IRI+5-FU/LV therapy. Estimated one-year overall survival rates were 26% with nal-IRI+5-FU/LV and 16% with 5-FU/LV. Baseline characteristics associated with long-term survival in the nal-IRI+5-FU/LV arm were Karnofsky performance status ≥90, age ≤65 years, lower CA19-9 levels, neutrophil-to-lymphocyte ratio ≤5 and no liver metastases. No new safety concerns were detected.

Conclusions: The survival benefits of nal-IRI+5-FU/LV versus 5-FU/LV were maintained over an extended follow-up, and prognostic markers of survival ≥1 year were identified.

Clinical trial registration number: NCT01494506.

Keywords: Liposomal irinotecan; Long-term survivors; NAPOLI-1; Pancreatic adenocarcinoma; Treatment outcome.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CA-19-9 Antigen
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / secondary
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Irinotecan / administration & dosage*
  • Karnofsky Performance Status
  • Leucovorin / administration & dosage
  • Liposomes
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Progression-Free Survival
  • Proportional Hazards Models


  • CA-19-9 Antigen
  • Liposomes
  • Irinotecan
  • Leucovorin
  • Fluorouracil

Associated data