TY - JOUR
T1 - Liposomal Irinotecan + 5-FU/LV in Metastatic Pancreatic Cancer
T2 - Subgroup Analyses of Patient, Tumor, and Previous Treatment Characteristics in the Pivotal NAPOLI-1 Trial
AU - MacArulla Mercadé, Teresa
AU - Chen, Li Tzong
AU - Li, Chung Pin
AU - Siveke, Jens T.
AU - Cunningham, David
AU - Bodoky, György
AU - Blanc, Jean Frédéric
AU - Lee, Kyung Hun
AU - Dean, Andrew
AU - Belanger, Bruce
AU - Wang-Gillam, Andrea
N1 - Funding Information:
The authors thank the patients, their families, all investigators, and support staff for their participation in this study. The NAPOLI-1 study (ClinicalTrials.gov identifier: NCT01494506) was sponsored by Merrimack Pharmaceuticals, Inc, Cambridge, MA. The analyses and first data presentation were done by Merrimack Pharmaceuticals, Inc. This post hoc analysis was sponsored by Shire. Rights for nal-IRI now reside with Ipsen in the US (since April 2017); PharmaEngine, Inc, holds the rights in Taiwan; Servier holds rights in the rest of the world through a licensing agreement with Ipsen. Bruce Belanger (Merrimack Pharmaceuticals, Inc, at the time of the study, now Ipsen) and Jie Chen (Shire plc, Cambridge, MA) were responsible for statistical analyses of the data. The authors acknowledge Beloo Mirakhur (former employee of Ipsen Bioscience Inc, Basking Ridge, NJ) for her valuable contributions to the development of this manuscript. Medical writing and editorial support was provided by Christopher A Lamb of Physicians World Europe GmbH, initially funded by Shire (Zug, Switzerland) and subsequently by Servier Global Medical Affairs (Suresnes, France). Although employees of the sponsor were involved in the design, collection, analysis, interpretation, fact checking of information, and coordination and collation of comments, the content of this manuscript, the interpretation of the data, and the decision to submit the manuscript for publication in Pancreas was made by the authors independently.
Publisher Copyright:
© 2020 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - irinotecan liposomal injection
KW - mPAC
KW - pancreatic cancer
KW - phase 3 clinical trial
KW - post hoc
KW - subanalysis
UR - http://www.scopus.com/inward/record.url?scp=85077073508&partnerID=8YFLogxK
U2 - 10.1097/MPA.0000000000001455
DO - 10.1097/MPA.0000000000001455
M3 - Article
C2 - 31856081
AN - SCOPUS:85077073508
SN - 0885-3177
VL - 49
SP - 62
EP - 75
JO - Pancreas
JF - Pancreas
IS - 1
ER -