Survival with nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in per-protocol and non-per-protocol populations of NAPOLI-1: Expanded analysis of a global phase 3 trial

Li Tzong Chen, Jens T. Siveke, Andrea Wang-Gillam, Chung Pin Li, György Bodoky, Andrew P. Dean, Yan Shen Shan, Gayle S. Jameson, Teresa Macarulla, Kyung Hun Lee, David Cunningham, Jean Frédéric Blanc, Chang Fang Chiu, Gilberto Schwartsmann, Fadi S. Braiteh, Khalid Mamlouk, Bruce Belanger, Floris A. de Jong, Richard A. Hubner

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24 Scopus citations

Abstract

Background: In the phase 3 randomised NAPOLI-1 clinical study, a 45% increase in median overall survival (OS) was shown with liposomal irinotecan, 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) versus 5-FU/LV in patients with metastatic pancreatic cancer progressing after gemcitabine-based therapy. Here, we report data from a pre-specified, expanded analysis of outcomes in the per-protocol (PP) population. Materials and methods: The PP population comprised patients receiving ≥80% of planned treatment during the first 6 weeks, with no major protocol violations. A post-hoc analysis of the non-PP population was also performed. Results: For PP patients, median OS was 8.9 (95% confidence interval: 6.4–10.5) months with nal-IRI+5-FU/LV (n = 66) vs 5.1 (4.0–7.2) months with 5-FU/LV (n = 71; unstratified hazard ratio [HR] 0.57, p = 0.011). For non-PP patients, it was 4.4 (3.3–5.3) months with nal-IRI+5-FU/LV (n = 51) vs 2.8 (1.7–3.2) months with 5-FU/LV (n = 48; unstratified HR 0.64, p = 0.0648). Conclusion: A statistically significant survival advantage was observed with nal-IRI+5-FU/LV vs 5-FU/LV in the PP patient population.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalEuropean Journal of Cancer
Volume105
DOIs
StatePublished - Dec 2018

Keywords

  • Clinical trial, phase III
  • Drug combinations, Antineoplastic
  • Gemcitabine
  • Neoplasm metastasis
  • Pancreatic neoplasms
  • Sensitivity and specificity
  • Survival analysis

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