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

Abstract

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.

• Authors: Andrea Wang-Gillam, Richard A Hubner, Jens T Siveke, Daniel D Von Hoff, Bruce Belanger, Floris A de Jong, Beloo Mirakhur, Li-Tzong Chen
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 108 Pg. 78-87 (02 2019) ISSN: 1879-0852 [Electronic] England
• PMID: 30654298 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

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

Topics

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