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Clinical Trial
. 2020 Jan;49(1):62-75.
doi: 10.1097/MPA.0000000000001455.

Liposomal Irinotecan + 5-FU/LV in Metastatic Pancreatic Cancer: Subgroup Analyses of Patient, Tumor, and Previous Treatment Characteristics in the Pivotal NAPOLI-1 Trial

Teresa Macarulla Mercadé  1 , Li-Tzong Chen, Chung-Pin Li, Jens T Siveke, David Cunningham  2 , György Bodoky  3 , Jean-Frédéric Blanc  4 , Kyung-Hun Lee  5 , Andrew Dean  6 , Bruce Belanger  7 , Andrea Wang-Gillam  8
Affiliations
Clinical Trial

Liposomal Irinotecan + 5-FU/LV in Metastatic Pancreatic Cancer: Subgroup Analyses of Patient, Tumor, and Previous Treatment Characteristics in the Pivotal NAPOLI-1 Trial

Teresa Macarulla Mercadé et al. Pancreas. 2020 Jan.

Erratum in

Abstract

Objectives: The NAnoliPOsomaL Irinotecan (NAPOLI-1) study (NCT01494506) was the largest global phase 3 study in a post-gemcitabine metastatic pancreatic adenocarcinoma (mPAC) population (N = 417). The subanalyses reported here investigated the prognostic effect of tumor characteristics and disease stage, prior treatment characteristics, baseline patient characteristics on survival outcomes in NAPOLI-1, and whether liposomal irinotecan (nal-IRI) + 5-fluorouracil/leucovorin (5-FU/LV) benefited patients with mPAC across subgroups.

Methods: Post hoc analyses were performed in the NAPOLI-1 population (4 across tumor characteristics and disease stage, 6 across prior treatment characteristics, and 4 across patient baseline characteristics). Survival outcomes were estimated by Kaplan-Meier analysis and patient safety data were evaluated.

Results: Mortality and morbidity risk was lower on nal-IRI+5-FU/LV treatment across subgroups. Exceptions were patients who had received prior nonliposomal irinotecan and those who had undergone prior Whipple procedure (overall survival hazard ratio = 1.25 and 1.23, respectively). Decreased appetite, liver metastases, and number of measurable metastatic lesions seemed to be prognostic of survival in this population. Subgroup safety data were generally comparable with those in the overall NAPOLI-1 safety population.

Conclusions: A diverse population of patients with mPAC that progressed on gemcitabine-based therapy benefited from nal-IRI+5-FU/LV versus 5-FU/LV, potentially helping guide treatment decisions for challenging cases.

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Conflict of interest statement

T.M.M. reports advisor roles for Shire, Servier, Celgene, Amgen, Incyte, Astra-Zeneca, and Sanofi. L.-T.C. reports an advisor role for ONO, Bristol Myers-Squibb, MSD, Eli Lilly, PhamaEngine, Five Prime, Novartis, and Astra Zeneca; honoraria from ONO, BMS, MSD, Eli Lilly, PhamaEngine, TTY, SyncoreBio, Five Prime, Novartis, Astra Zeneca, and Ipsen; and research funding from Novartis, Pfizer, Merck Serono, Polaris, TTY, SyncoreBio, and Celgene. J.T.S. reports an advisor role for Baxalta (now part of Shire), Celgene, Roche, and Shire; honoraria from Shire and Celgene; and research funding from 4SC, Celgene, Bristol Myers-Squibb, and Roche. D.C. reports research funding from Amgen, AstraZeneca, Bayer, Celgene, Merrimack, Medimmune, Merck Serono, and Sanofi. G.B. reports honoraria received from Servier, Roche, Bayer, Pfizer, Janssen, Novartis, and Lilly and advisor role for Bayer, Roche, Pfizer, Janssen, Novartis, Lilly, Taiho, and Nordic. J.-F.B. reports an advisor role for Baxalta (now part of Shire) and Shire. A.D. reports honoraria received from Specialised Therapeutics Australia and consultant/advisor roles for Baxalta (now part of Shire) and Celgene. B.B. was employed by Merrimack Pharmaceuticals, Inc, at the time of the study, and is currently an employee at Ipsen Bioscience, Inc, A.W.-G. reports consultant/advisor roles for Merrimack, Pfizer, Newlink Genetics, Ipsen, and Jacobio and research funding from Newlink Genetics, Precision Therapeutics, AstraZeneca, Aduro Biotech, EMD Serono, Pfizer, Halozyme, Oncomed, CTI, Lilly, Abbvie, Plexxikon, Verastem, Merck, and BioMed Vally Discoveries. The other authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
NAPOLI-1 trial design and subgroup analyses. *The study was amended to add the nal-IRI+5-FU/LV arm once safety data on the combination became available. Only those patients enrolled in the 5-FU/LV arm after the amendment (n = 119) were used as the control for the combination arm (trial registered at ClinicalTrials.gov, NCT01494506). Abbreviation Q2W, every 2 weeks; Q3W, every 3 weeks; Q6W, every 6 weeks; SD, stable disease.
FIGURE 2
FIGURE 2
Overall survival in NAPOLI-1 by baseline liver lesions (ITT population). Patients with baseline liver lesion data available were included in this analysis.
FIGURE 3
FIGURE 3
Mortality in patients with increased baseline pain and analgesic use. A, Overall survival based on baseline pain subgroups; mean value for baseline pain is 25. B, Overall survival based on baseline analgesic use subgroups; median baseline analgesic use is 8.1 mg/d. *Patients with baseline pain intensity data available (includes all treatment arms). †Patients with baseline analgesic use data available (includes all treatment arms).
FIGURE 4
FIGURE 4
Survival outcomes in patients with decreased appetite at baseline in the NAPOLI-1 ITT population. A, Overall survival in patients with or without decreased appetite at baseline. B, Progression-free survival in patients with or without decreased appetite at baseline.
FIGURE 5
FIGURE 5
Survival outcomes in patients with or without prior irinotecan-based therapy treated with nal-IRI+5-FU/LV or 5-FU/LV. A, Overall survival, no prior irinotecan. B, Overall survival, prior irinotecan. C, Progression-free survival, no prior irinotecan. D, Progression-free survival, prior irinotecan. NR, not reached.
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