323P - NALIRIFOX versus nab-paclitaxel and gemcitabine (Gem+NabP) in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Subgroup analysis of patients aged 65 years or older in NAPOLI 3

Background

In NAPOLI 3 (NCT04083235), a global, randomized, open-label phase 3 study, NALIRIFOX significantly improved median overall survival (mOS; primary endpoint) and median progression-free survival (mPFS) vs Gem+NabP in patients (median [range] age, 65.0 [20–85] years) with untreated mPDAC. Although mPDAC is commonly diagnosed in patients aged 65–70 years, older patients are often underrepresented in clinical trials and may be ineligible for available treatments. Here, we present additional results from NAPOLI 3 in patients aged ≥ 65 years (prespecified subgroup) and ≥ 70 years.

Methods

Eligible patients with untreated mPDAC were randomized (1:1) to receive liposomal irinotecan 50 mg/m² + oxaliplatin 60 mg/m² + leucovorin 400 mg/m² + 5-fluorouracil 2400 mg/m² (NALIRIFOX) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m² (Gem+NabP) on days 1, 8 and 15 of a 28-day cycle. Efficacy and safety analyses were performed in the intent-to-treat (ITT) and safety populations, respectively. Time-to-event endpoints were evaluated using Kaplan–Meier methods.

Results

Of 770 randomized patients, 50.1% and 28.2% were aged ≥ 65 years and ≥ 70 years, respectively. Baseline characteristics were generally balanced. OS and PFS outcomes were numerically improved with NALIRIFOX vs Gem+NabP in both subgroups (Table). Similar proportions of patients (50.8% vs 52.6% [≥ 65 years] and 44.7% vs 47.7% [≥ 70 years]) in the NALIRIFOX vs Gem+NabP groups (safety population) received subsequent anticancer therapy. Key safety data are shown in the table. Table: 323P

Conclusions

Outcomes in patients aged ≥ 65 years and ≥ 70 years were consistent with those of the overall NAPOLI 3 population and confirm NALIRIFOX as a suitable treatment option for older patients; however, results should be interpreted with caution owing to low patient numbers.

Clinical trial identification

NCT04083235.

Editorial acknowledgement

Medical writing support was provided by Emma Bolton, D.Phil., of Oxford PharmaGenesis, Oxford, UK which was sponsored by Ipsen.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

T. Macarulla Mercade: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd., Celgene SLU, Eisai, Ipsen Pharma, Incyte; Financial Interests, Personal, Other, Direct research fund: Servier, Merck, Sharp and Dohme, Novocure, QED Therapeutics Inc, Roche, Sanofi-Aventis, Zymeworks; Financial Interests, Personal, Invited Speaker: Lilly, Janssen; Financial Interests, Institutional, Research Grant: Amc Medical Research, Armo Biosciences, Basilea, Biokeralty Research Institute, Merck Sharp & Dohme, Oncomed Pharmaceuticals, QED Therapeutics, VCN Biosciences, AbbVie Farmaceútica, Ability Pharmaceuticals, Agios, Amgen, Aslan, AstraZeneca, Bayer, BeiGene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, FibroGen, Genentech, Hallozyme, Immunomedics, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, MedImmune, Merimarck, Millenim, Nelum, Novartis, Novocure, Pfizer, Pharmacyclics, Roche, Zymeworks; Non-Financial Interests, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO; Other, Editorial Board: GI Annals og¡f Oncology. R.A. Pazo Cid: Financial Interests, Personal, Advisory Board: Roche, BMS, Servier, Ipsen; Financial Interests, Personal, Invited Speaker: Servier, BMS, Roche, Eisai; Financial Interests, Personal, Expert Testimony: Lilly, AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, Support for manuscript presentation (funding, provision of study materials, medical writing, article processing charges): Ipsen, Astellas. V. Chung: Financial Interests, Personal, Other, Consultant: Perthera; Financial Interests, Institutional, Research Grant, Funding for investigator sponsored trial: Merck. A.S. Paulson: Financial Interests, Personal, Full or part-time Employment, Spouse: Day One; Financial Interests, Personal, Stocks/Shares: Actinium; Financial Interests, Personal, Invited Speaker, Honoraria: Cardinal Health, Curio Science; Financial Interests, Personal, Advisory Role: AADI Bioscience, Advanced Accelerator Applications, Amgen, Astellas Pharma, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, Hutchison MediPharma, Incyte, Ipsen, Eli Lilly and Company, Mirati Therapeutics, Pfizer, Agenus, Servier; Financial Interests, Personal, Speaker’s Bureau: IDEO oncology; Financial Interests, Institutional, Funding: AstraZeneca, Bayer, Bristol Myers Squibb, Camurus, Deciphera, Exelixis, GI Therapeutics, Hutchison MediPharma, Incyte, Innovative Cellular Therapeutics, Ipsen, Eli Lilly and Company, Merck, NuCana, Relay Therapeutics, Seagen, SOTIO Biotech, Taiho Pharmaceutical, Tempus, Zentalis Pharmaceuticals; Financial Interests, Personal, Other, Travel/accommodation expenses: Pfizer. S. Pant: Financial Interests, Personal, Other, Zymeworks: Zymeworks; Financial Interests, Personal, Other, Ipsen: Ipsen; Financial Interests, Personal, Other, Novartis: Novartis; Financial Interests, Personal, Other, Janssen: Janssen; Financial Interests, Personal, Other, Boehringer Ingelheim: Boehringer Ingelheim; Financial Interests, Personal, Other, AskGene Pharma; Financial Interests, Institutional, Funding, Company: Mirati Therapeutics Recipient: Your Institution: Mirati Therapeutics; Financial Interests, Institutional, Invited Speaker, Company: Lilly Recipient: Your Institution: Lilly; Financial Interests, Institutional, Invited Speaker, Company: Xencor Recipient: Your Institution: Xencor; Financial Interests, Institutional, Invited Speaker, Company: Novartis Recipient: Your Institution: Novartis; Financial Interests, Institutional, Invited Speaker, Company: Rgenix Recipient: Your Institution: Rgenix; Financial Interests, Institutional, Invited Speaker, Company: Bristol Myers Squibb Recipient: Your Institution: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, Company: Astellas Pharma Recipient: Your Institution: Astellas Pharma; Financial Interests, Institutional, Invited Speaker, Company: Frame wave Recipient: Your Institution: Company: Framewave Recipient: Your Institution; Financial Interests, Institutional, Invited Speaker, Company: 4D Pharma Recipient: Your Institution: 4D Pharma; Financial Interests, Institutional, Invited Speaker, Company: Boehringer Ingelheim Recipient: Your Institution: Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker, Company: NGM Biopharmaceuticals Recipient: Your Institution: NGM Biopharmaceuticals; Financial Interests, Institutional, Invited Speaker, Company: Janssen Recipient: Your Institution: Janssen; Financial Interests, Institutional, Invited Speaker, Company: Arcus Biosciences Recipient: Your Institution: Arcus Biosciences; Financial Interests, Institutional, Invited Speaker, Company: Elicio Therapeutics Recipient: Your Institution: Elicio Therapeutics; Financial Interests, Institutional, Invited Speaker, Company: Bionte Recipient: Your Institution: Bionte; Financial Interests, Institutional, Invited Speaker, Company: Ipsen Recipient: Your Institution: Ipsen; Financial Interests, Institutional, Invited Speaker, Company: Zymeworks Recipient: Your Institution: Zymeworks; Financial Interests, Institutional, Invited Speaker, Company: Pfizer Recipient: Your Institution: Pfizer; Financial Interests, Institutional, Invited Speaker, Company: ImmunoMET Recipient: Your Institution: ImmunoMET; Financial Interests, Institutional, Invited Speaker, Company: Immuneering Recipient: Your Institution: Immuneering; Financial Interests, Institutional, Invited Speaker, Company: Amal Therapeutics Recipient: Your Institution: Amal Therapeutics. E.M. O'Reilly: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, BioNTech, Merck, AstraZeneca, Novartis, FibroGen, Astellas, Tempus, Merus, BMS, Berry Genomics, Exelixis, Incyte, Neogene, Sevier, Thetis, Vector, Yiviva; Financial Interests, Personal, Advisory Board, +Spouse: Ipsen; Financial Interests, Personal, Advisory Board, Spouse: Genentech/Roche, Eisai; Financial Interests, Personal, Advisory Board, + spouse: Autem; Financial Interests, Institutional, Invited Speaker: Genentech/Roche, Arcus, Elicio, AstraZeneca, Pertzye; Financial Interests, Personal and Institutional, Invited Speaker: BioNTech; Financial Interests, Institutional, Research Grant: Parker Institute; Non-Financial Interests, Other, Scientific and Medical Advisory Board: Pancreas Cancer Action Network; Non-Financial Interests, Member of Board of Directors: National Pancreas Foundation; Other, Editor: American Society of Clinical Oncology, American Association of Cancer Research (AACR). R. Hubner: Financial Interests, Personal, Expert Testimony: Novartis, AstraZeneca; Financial Interests, Personal, Other, Clinical trial steering committee membership: Ipsen, BeiGene; Other, Conference attendance funding: Roche. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, Agenus, ALX, Arcus Biosciences, Astellas, AstraZeneca, Bayer, BeiGene, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Debiopharm, Elmedix, Eisai, GSK, Hoopika Biotech, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Seattle Genetics, Servier, Simcere, Takeda, Taiho, Terumo; Financial Interests, Personal, Invited Speaker: Amgen, Pfizer. T. Bekaii-Saab: Financial Interests, Institutional, Advisory Board: Bayer, Pfizer, Incyte, Ipsen, Seattle Genetics, Genentech, Merck KGA, Merus, Eisai, Servier; Financial Interests, Institutional, Other, DSMB: Merck; Financial Interests, Personal, Advisory Board: AbbVie, Boehringer Ingelheim, Janssen, AstraZeneca, Daiichi Sankyo, Natera, Celularity, Exact Science, Sobi, BeiGene, Xilis, Foundation Medicine, Stemline, Blueprint, Celularity, Caladrius, Glaxo SmithKline, Deciphera, Zai Labs, Illumina, Sanofi; Financial Interests, Personal, Other, DSMB: AstraZeneca, Exelixis, The Valley Hospital, FibroGen; Financial Interests, Personal, Other, DSMC: PanCAN; Financial Interests, Personal, Royalties, WO/2018/183488: human PD1 peptide vaccines and uses thereof – Licensed to Imugene: Imugene; Financial Interests, Personal, Royalties, WO/2019/055687: methods and compositions for the treatment of cancer cachexiA – Licensed to Recursion: Recursion; Financial Interests, Institutional, Research Grant: Agios, Arys, Bayer, Amgen, Ipsen, Clovis, Pfizer, Celgene, Novartis, Arcus, Atreca, Mirati, Merus, Abgenomics, BMS; Financial Interests, Institutional, Invited Speaker: Boston Biomedical, Incyte, Seattle Genetics; Non-Financial Interests, Advisory Role: Imugene, Sun Biopharma. L. Zhang: Financial Interests, Personal, Full or part-time Employment: Ipsen; Financial Interests, Personal, Stocks/Shares: Ipsen. J. Li: Financial Interests, Personal, Full or part-time Employment: Ipsen. H.(. Chen: Financial Interests, Personal, Full or part-time Employment: Ipsen; Financial Interests, Personal, Stocks/Shares: Bayer, Moderna. F. Maxwell: Financial Interests, Personal, Full or part-time Employment: Ipsen; Financial Interests, Personal, Research Grant: Ipsen. Z.A. Wainberg: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Arcus, Bayer, AstraZeneca, Novartis, Roche, Ipsen, Daiichi Sankyo, Merck, BMS, Merus; Financial Interests, Personal, Other, DMC: Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis, Ipsen, Merck, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, Arcus. D. Melisi: Financial Interests, Personal, Advisory Board: Incyte Co., Servier, iOnctura, Tahio; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Research Grant: iOnctura. All other authors have declared no conflicts of interest.