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Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer - A subgroup analysis of the pivotal NAPOLI-1 trial Blanc, Jean-Frédéric Wang-Gillam, Andrea Chen, Li-Tzong Siveke, Jens T. Mirakhur, Beloo Macarulla Mercadé, Teresa Institut Català de la Salut [Macarulla T] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Blanc JF] Pôle ADEN, Hôpital Haut-Lévêque, CHU Bordeaux, Bordeaux, France. [Wang-Gillam A] Division of Oncology, Washington University in St. Louis, MO, USA. [Chen LT] National Institute of Cancer Research, National Health Research Institutes, National Cheng Kung University, Tainan, Taiwan. Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan. [Siveke JT] Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. Cancer Consortium (DKTK, partner site Essen), German Cancer Research Center, DKFZ, Heidelberg, Germany. [Mirakhur B] Ipsen Biopharmaceuticals, Inc., Cambridge, MA, United States Vall d'Hebron Barcelona Hospital Campus Pàncrees - Càncer Metàstasi Medicaments - Administració DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms CHEMICALS AND DRUGS::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil Other subheadings::Other subheadings::Other subheadings::/administration & dosage DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas COMPUESTOS QUÍMICOS Y DROGAS::compuestos heterocíclicos::compuestos heterocíclicos de 1 anillo::pirimidinas::pirimidinonas::uracilo::fluorouracilo Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica Irinotecan liposomal; Pacients grans; Càncer de pàncrees Irinotecán liposomal; Pacientes mayores; Cáncer de páncreas Liposomal irinotecan; Older patients; Pancreatic cancer Objectives Pancreatic cancer is a highly lethal disease predominantly affecting older patients. Characterization of outcomes in these patients may help optimise treatment decisions. The global, phase 3 NAPOLI-1 trial ( NCT01494506 ) demonstrated an overall survival (OS) benefit with liposomal irinotecan and 5-flurouracil/leucovorin (nal-IRI + 5-FU/LV) versus 5-FU/LV. This subgroup analysis explored impact of age on outcomes in NAPOLI-1 patients, and nal-IRI + 5-FU/LV efficacy and safety in older patients. Materials and Methods This exploratory, post-hoc analysis of the NAPOLI-1 trial included patients aged ≥eighteen years (no upper limit) with metastatic pancreatic adenocarcinoma that had progressed on gemcitabine-based therapy. Patients were stratified by age (cut-offs at 65, 70, and 75 years); OS and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results Of 417 randomized patients, 192 (46%), 110 (26%) and 43 (10%) were aged ≥65, ≥70 and ≥ 75 years, respectively. Mortality risk and risk of disease progression were similar in older and younger patients independent of treatment (HRs for median [m]OS/mPFS comparisons were 0.88/0.95 [<65 versus ≥65 years], 0.89/0.88 [<70 versus ≥70 years] and 1.04/0.98 [<75 versus ≥75 years]; P > .25). Reduced mortality/morbidity risk with nal-IRI + 5-FU/LV in older subgroups was in line with the wider population. No additional toxicities with nal-IRI + 5-FU/LV were observed in older patients: 86% of patients ≥75 years versus 69% <75 years required a dose delay or reduction due to toxicities (43% versus 32% dose reductions). Discussion Results suggest that older patients with metastatic pancreatic adenocarcinoma that progressed on prior gemcitabine-based treatment can benefit from second-line therapy, supporting nal-IRI + 5-FU/LV treatment in older patients. The NAPOLI-1 trial (ClinicalTrials.govidentifier: NCT01494506) was sponsored by Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA; Medical writing support was provided by Laura McMahon of Physicians World Europe GmbH, Mannheim, Germany, and funded by Shire International, Zug, Switzerland. Correction and publication costs were funded by Global Medical Affairs, Servier, Suresnes, France. 2021-03-19T12:33:13Z 2021-03-19T12:33:13Z 2019-05-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Macarulla T, Blanc JF, Wang-Gillam A, Chen LT, Siveke JT, Mirakhur B, et al. Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer – A subgroup analysis of the pivotal NAPOLI-1 trial. J Geriatr Oncol. 2019 May 1;10(3):427–35. 1879-4068 https://hdl.handle.net/11351/5777 10.1016/j.jgo.2019.02.011 30842038 000470049200012 eng Journal of Geriatric Oncology;10 https://linkinghub.elsevier.com/retrieve/pii/S1879-4068(18)30349-7 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf Elsevier Scientia