First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study
- PMID: 33957442
- DOI: 10.1016/j.ejca.2021.03.028
First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study
Abstract
Background: This open-label, phase I/II study evaluated safety and efficacy for first-line liposomal irinotecan + oxaliplatin + 5-fluorouracil + leucovorin (NALIRIFOX).
Methods: Patients (aged ≥18 years) had locally advanced/metastatic pancreatic ductal adenocarcinoma (mPDAC), with an Eastern Cooperative Oncology Group performance status score of 0/1 and adequate organ function. Primary objectives were to determine the maximum tolerated dose (MTD) and to evaluate safety and tolerability. Treatment-emergent adverse events (TEAEs) were graded using National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. Efficacy end-points included progression-free survival (PFS) and overall survival (OS); disease assessments used Response Evaluation Criteria in Solid Tumors 1.1.
Results: The MTD (liposomal irinotecan 50 mg/m2 [free-base equivalent], oxaliplatin 60 mg/m2, 5-fluorouracil 2400 mg/m2, leucovorin 400 mg/m2 every 2 weeks) was based on dose-limiting toxicities and cumulative safety data in four dose-exploration cohorts. The MTD was received by 32 of 56 patients, seven during dose exploration and 25 during dose expansion (median age 58.0 years [range, 39-76], 28 [87.5%] with metastatic disease at diagnosis [29 at study entry], and one receiving study treatment at data cutoff [26 February 2020]). Of these patients, 22 of 32 had grade ≥3 treatment-related TEAEs, most commonly neutropenia (31.3%), febrile neutropenia (12.5%) and hypokalaemia (12.5%); ten had serious treatment-related TEAEs; and three died from TEAEs considered unrelated to treatment. Median PFS and OS were 9.2 (95% CI: 7.69-11.96) and 12.6 (8.74-18.69) months, respectively.
Conclusion: First-line NALIRIFOX for patients with locally advanced/mPDAC was generally manageable and tolerable. A randomised, controlled phase III study is underway.
Trial registration: ClinicalTrials.gov NCT02551991.
Keywords: Clinical trial (MeSH: ‘clinical trials as topic’); Liposomal irinotecan; Locally advanced pancreatic adenocarcinoma; Metastatic pancreatic adenocarcinoma (MeSH: ‘pancreatic neoplasms’, ‘carcinoma, pancreatic ductal’, ‘neoplasm metastasis’); NALIRIFOX (MeSH: ‘Irinotecan’).
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Note: relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Zev A. Wainberg: Consulting or Advisory Role: AstraZeneca, Bayer, Daiichi Sankyo, Eli Lilly, Five Prime Therapeutics, Ipsen, Merck, QED Therapeutics, Research Funding: Five Prime Therapeutics (Inst), Ipsen (Inst), Novartis (Inst), Plexxikon (Inst). Tanios Bekaii-Saab: 1Globe Health Institute, AbGenomics, Amgen, Array BioPharma, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Biomedical, Bristol-Myers Squibb, Celgene, Clovis Oncology, Eli Lilly, Exelixis, Genentech, Immuneering, Imugene, Incyte, Ipsen, Merck, Pancreatic Cancer Action Network (PanCAN), Seattle Genetics, Sobi, Sun BioPharma, Treos Bio. Patrick M. Boland: Consulting or Advisory Role: Bayer, Merrimack Pharmaceuticals; honoraria: Sirtex Medical, Research Funding: Advaxis, Bayer, Boehringer Ingelheim, Boston Biomedical, Cascadian Therapeutics, Genentech, Merck Farshid Dayyani: Research Funding: Amgen (Inst), AstraZeneca (Inst), Bristol-Myers Squibb (Inst), Exelixis (Inst), Ipsen (Inst), Taiho Pharmaceutical (Inst), Consulting or Advisory Role: Eisai, Exelixis, Foundation Medicine, Genentech, Ipsen, Natera (Signatera), QED Therapeutics, Speakers’ Bureau: Amgen, Deciphera Pharmaceuticals, Eisai, Exelixis, Ipsen, Natera (Signatera), Sirtex Medical, Employment: Roche Diagnostics (I). Teresa Macarulla: Honoraria: Eli Lilly, Ipsen, Roche, Sanofi, Sanofi Genzyme, Shire, Tesaro, Research Funding: AstraZeneca, Agios, Aslan Pharmaceuticals, Bayer, Biogen, Celgene, Eli Lilly, Genentech, Halozyme Therapeutics, Immonomedics, Merrimack Pharmaceuticals, Millennium Pharmaceuticals, Novartis, Novocure, OncoMed Pharmaceuticals, Pfizer, Pharmacyclics, Roche, Consulting or Advisory Role: Baxalta, Celgene, H3 Biomedicine, Incyte, QED Therapeutics, Sanofi Genzyme, Shire, Servier, Speakers’ Bureau: Celgene, Sanofi, Shire, Travel, Accommodation, Expenses: Bayer, H3 Biomedicine, Merck, Sanofi. Kabir Mody: Research Funding: Agios, ArQule, AstraZeneca, Genentech, Incyte, Puma Biotechnology, Senwa Biosciences, Taiho Pharmaceutical, NCI of the NIH award # NCI/NIH P50 CA210964, Consulting or Advisory Role: AstraZeneca, Bayer, Celgene, Eisai, Exelixis, Ipsen, Merrimack Pharmaceuticals, Vicus Therapeutics. Bruce Belanger: Former employee: Ipsen. Fiona Maxwell: Employment: Ipsen, Stock and Other Ownership Interests: Ipsen. Yan Moore: Employment: Ipsen, Stock and Other Ownership Interests: Ipsen, Leadership: Ipsen. Arunthathi Thiagalingam: Former employee: Ipsen, Stock and Other Ownership Interests: Ipsen. Tiffany Wang: Employment: Ipsen, Stock and Other Ownership Interests: Ipsen. Bin Zhang: Employment: Ipsen, Stock and Other Ownership Interests: Ipsen, Patents, Royalties, Other Intellectual Property: Ipsen. Andrew Dean: Consulting or Advisory Role: Shire (not compensated), Specialised Therapeutics (not compensated), Travel, Accommodation, Expenses: Amgen.
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