Liposomal irinotecan (nal-IRI) plus 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) progressing on gemcitabine-b...

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Pancreatic Cancer
Presenter Li-Tzong Chen
Citation Annals of Oncology (2018) 29 (suppl_9): ix46-ix66. 10.1093/annonc/mdy432
Authors L. Chen1, T. Macarulla Mercadé2, K. Lee3, G. Lakatos4, A. Wang-Gillam5, B. Mirakhur6, F. de Jong7
  • 1National Institute Of Cancer Research, National Health Research Institutes, 704 - Tainan/TW
  • 2Medical Oncology Department, Vall d’Hebron University Hospital (HUVH), Barcelona/ES
  • 3Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 4Department Of Oncology, Szent Laszlo Korhaz, 1097 - Budapest/HU
  • 5Division Of Oncology, Washington University in St. Louis, St. Louis/US
  • 6-, Ipsen - Basking Ridge, Basking Ridge/US
  • 7-, Shire, 6300 - Zug/CH



NAPOLI-1 (NCT01494506) was a global phase 3 trial of pts with mPDAC that progressed following gemcitabine-based therapy. Median OS (mOS) for nal-IRI+5-FU/LV was 6.1 vs 4.2 months (mo) for 5-FU/LV (unstratified HR = 0.67; P = 0.012). Here, we present four separate post-hoc subgroup analyses exploring baseline (BL) parameters.


We evaluated outcomes in pts with or without BL metabolism and nutrition disorders (hypercholesterolemia and decreased appetite [=anorexia, poor appetite, lack of appetite and loss of appetite]), by primary tumour location (PTL), with or without a biliary stent at BL, and by best response to prior therapy (complete response/partial response [CR/PR] vs not-CR/PR, and CR/PR/stable disease [CR/PR/SD] vs not-CR/PR/SD).


For ITT pts, decreased appetite at BL significantly reduced mOS (n = 77) vs without (n = 340) (3.6 vs 5.3 mo; HR = 1.65; P < 0.001). We observed a trend for lower mOS with hypercholesterolemia. PTL (e.g. incl./excl. pancreatic head) had no prognostic effect on mOS after trial inclusion (HRs=0.87–1.06). ITT pts with (n = 37) and without (n = 380) biliary stent at BL had comparable mOS (5.3 vs 4.8 mo; HR = 0.97). Pts with (n = 15) and without stent (n = 102) and receiving nal-IRI+5-FU/LV had similar mOS (6.2 vs 6.1 mo; HR = 0.44). mOS in pts with CR/PR was 5.6 mo vs 4.8 mo in not-CR/PR (HR = 0.73). CR/PR/SD was similar to not-CR/PR/SD (mOS both 4.9 mo, HR = 0.95). Pts with nal-IRI+5-FU/LV with CR/PR (n = 11) had a mOS of 9.3 mo vs 6.1 mo in not-CR/PR (n = 106; HR = 0.64).

mOS in CR/PR/SD and non-CR/PR/SD was similar (HR = 1.04). mOS and mPFS were increased with nal-IRI+5-FU/LV for all subgroups vs 5-FU/LV (those with n > 10 per arm). Within subgroups, drug-related AEs and dose modifications/discontinuations were generally comparable to NAPOLI-1.


Decreased appetite at BL was prognostic for survival in NAPOLI-1 pts. We found no significant prognostic effect of other subgroups in either the NAPOLI-1 ITT or the nal-IRI+5-FU/LV treatment populations on survival after trial inclusion. Pts benefitted from nal-IRI+5-FU/LV treatment vs 5-FU/LV across subgroups.

Editorial acknowledgement

Florian Szardenings of Physicians World Europe GmbH, Mannheim, Germany, and funded by Shire, Zug, Switzerland.

Clinical trial identification


Legal entity responsible for the study

Merrimack Pharmaceuticals Inc.


The NAPOLI-1 study ( identifier: NCT01494506) was sponsored by Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA. This post-hoc analysis was sponsored by Shire.


L-T. Chen: Honoraria and/or consultant/advisor: Bristol-Myers Squibb, Ono Pharmaceutical, Lilly, MSD, PharmaEngine, Merrimack Pharmaceuticals, TTY Biopharm, SynCoreBio, Five Prime, Novartis; Patent with Hunilife Technology; Research Funding Novartis, GlaxoSmithKline, Merck Serono, TTY Biopharm, Polaris, SyncoreBio, Pfizer, Celgene. A. Wang-Gillam: Consultant/Advisor: Ipsen, Jacobio, Merrimack Pharmaceuticals, Pfizer, NewLink Genetics; Research Funding NewLink Genetics, Precision Therapeutics, AstraZeneca, Aduro Biotech, EMD Serono, Pfizer, Halozyme, OncoMed, CTI, Lilly, AbbVie, Plexxikon, Verastem, Merck, Biomed Valley Discoveries and Roche. T. Macarulla Mercadé: Consultant/advisor: Shire. B. Mirakhur: Employee: Ipsen, Stockholder: Ipsen and GlaxoSmithKline. F. de Jong: Employee: Servier; Stockholder: Shire. All other authors have declared no conflicts of interest.