@article{64ed96668636461383e5f80ca3e56ae8,
title = "Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study",
abstract = "The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P =.012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal-IRI+5-FU/LV (n = 34) had significantly longer median OS versus 5-FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P =.025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV versus 5-FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P =.011), and increased ORR (8.8% vs 0; P =.114). nal-IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5-FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P =.423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P =.155). Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).",
author = "Bang, {Yung Jue} and Li, {Chung Pin} and Lee, {Kyung Hun} and Chiu, {Chang Fang} and Park, {Joon Oh} and Shan, {Yan Shen} and Kim, {Jun Suk} and Chen, {Jen Shi} and Shim, {Hyun Jeong} and Rau, {Kun Ming} and Choi, {Hye Jin} and Oh, {Do Youn} and Bruce Belanger and Chen, {Li Tzong}",
note = "Funding Information: Yung‐Jue Bang reports a consulting/advisory role for AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serono, Bayer, BMS, Eli Lilly, Taiho, Daiichi‐Sankyo, Astellas, BeiGene, GreenCross, Samyang Biopharm, Hanmi, Genexine, and Shire; research grants (to the institution for clinical trials) from AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serono, Bayer, BMS, GSK, Pfizer, Eli Lilly, Boehringer‐Ingelheim, MacroGenics, Boston Biomedical, FivePrime, Curis, Taiho, Takeda, Ono, Daiichi Sankyo, Astellas, BeiGene, Green Cross, CKD Pharma, and Genexine. Chung‐Pin Li reports no disclosures. Kyung‐Hun Lee reports an advisor role for AstraZeneca, Bayer, Eisai, Ono Pharmaceuticals, Roche and Samsung Bioepis; honoraria from AstraZeneca and Roche. Chang‐Fang Chiu reports no disclosures. Joon Oh Park reports an advisor role for Shire. Yan‐Shen Shan reports no disclosures. Jun Suk Kim reports no disclosures. Jen‐Shi Chen reports no disclosures. Hyun‐Jeong Shim reports no disclosures. Kun‐Ming Rau reports no disclosures. Hye Jin Choi reports no disclosures. Do‐Youn Oh reports an advisor/consultant role for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymework, and Shire; research grants from AstraZeneca, Novartis, Array, Eli Lilly, and Green Cross. Bruce Belanger was employed by Merrimack Pharmaceuticals, Inc., at the time of the study, and is currently an employee at Ipsen Bioscience, Inc. Li‐Tzong Chen reports honoraria from Eli Lilly, Novartis, Bristol‐Myers‐Squibb, Ono Pharmaceutical, TTY Biopharm, PharmaEngine, MSD, Syncore Bio, Five Prime, AstraZeneca, and Ipsen; a consultant or advisor role for Eli Lilly, Novartis, Bristol‐Myers‐Squibb, Ono Pharmaceutical, PharmaEngine, MSD, Five Prime, AstraZeneca; and research funding from Novartis, Merck Serono, TTY Biopharm, SynCoreBio, Polaris, Celgene, and Pfizer. Funding Information: The authors would like to thank the patients, their families, all investigators and support staff for their participation in this study. Rights for nal‐IRI now reside with Ipsen in the USA (April 2017); PharmaEngine, Inc. holds the rights in Taiwan; Servier holds rights in the rest of the world. Bruce Belanger (Merrimack Pharmaceuticals, Inc., at the time of study, now Ipsen) was responsible for statistical analyses of this post‐hoc study. The authors acknowledge Beloo Mirakhur (former employee of Ipsen Bioscience Inc., Basking Ridge, NJ, USA) for her valuable contributions to the development of this manuscript. Medical writing support was provided by Florian Szardenings of Physicians World Europe GmbH (Mannheim, Germany), initially funded by Shire (Zug, Switzerland) and subsequently by Servier Global Medical Affairs (Suresnes, France). Funding Information: Funding information The NAPOLI-1 study (ClinicalTrials.gov identifier: NCT01494506) was sponsored by Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA. This post-hoc analysis was sponsored by Shire. 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 Cancer Science was made by the authors independently. The authors would like to thank the patients, their families, all investigators and support staff for their participation in this study. Rights for nal-IRI now reside with Ipsen in the USA (April 2017); PharmaEngine, Inc. holds the rights in Taiwan; Servier holds rights in the rest of the world. Bruce Belanger (Merrimack Pharmaceuticals, Inc., at the time of study, now Ipsen) was responsible for statistical analyses of this post-hoc study. The authors acknowledge Beloo Mirakhur (former employee of Ipsen Bioscience Inc., Basking Ridge, NJ, USA) for her valuable contributions to the development of this manuscript. Medical writing support was provided by Florian Szardenings of Physicians World Europe GmbH (Mannheim, Germany), initially funded by Shire (Zug, Switzerland) and subsequently by Servier Global Medical Affairs (Suresnes, France). Publisher Copyright: {\textcopyright} 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2020",
month = feb,
day = "1",
doi = "10.1111/cas.14264",
language = "English",
volume = "111",
pages = "513--527",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "2",
}