1619P - Health-related quality of life with nalirifox versus nab-paclitaxel + gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): EORTC QLQ-C30 results from the NAPOLI 3 trial

Background

The phase III NAPOLI 3 trial (NCT04083235) included 770 patients with mPDAC who were randomized (1:1) to receive liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) or nab-paclitaxel + gemcitabine (Gem+NabP) in 28-day cycles. As previously reported, at a median follow-up of 16.1 months, NALIRIFOX demonstrated statistically significant improvements in overall survival and progression-free survival versus Gem+NabP. Here, we report EORTC QLQ-C30 results from NAPOLI 3.

Methods

The EORTC QLQ-C30 was completed at baseline, day 1 of each 28-day cycle and at the end of treatment. A mixed model repeated measures (MMRM) model was used to describe the global health status (GHS) evolution over time between treatment arms. Time until definitive deterioration (TUDD) was defined as the time between randomization and first occurrence of a decrease ≥ 10 points in QLQ-C30 score without further improvement of ≥ 10 points or further data due to discontinuation.

Results

Mean GHS scores at baseline were similar between treatment arms (NALIRIFOX 62.1; Gem+NabP 61.2); from week 16, there was a trend towards improvement in GHS scores in the NALIRIFOX arm relative to the Gem+NabP arm. The median TUDD of GHS was 15.7 months with NALIRIFOX and 12.2 months with Gem+NabP (stratified Cox hazard ratio 0.74 [95% confidence interval: 0.53–1.04]; nominal p = 0.08). At 6 months, 26.4% and 31.7% of patients NALIRIFOX and Gem+NabP arms, respectively, experienced definitive deterioration in GHS. The TUDD of physical, role and emotional functioning, pain, dyspnea and constipation were longer, with nominal p ≤ 0.05, in patients who received NALIRIFOX versus Gem+NabP.

Conclusions

NALIRIFOX was associated with a trend towards improvement in GHS scores and longer TUDD in several EORTC QLQ-C30 subscales compared with Gem+NabP. However, these results should be interpreted with caution owing to the number of missing assessments.

Clinical trial identification

NCT04083235.

Editorial acknowledgement

Medical writing support provided by Emma Bolton PhD, Oxford PharmaGenesis.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

D. Melisi: Financial Interests, Personal, Advisory Board: Incyte co., Servier, iOnctura; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Research Grant: iOnctura. T. Macarulla: 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 Dhome, 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, AstraZecena, 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, Novocure, Millenim, Nelum, Novartis, Zymeworks, Pfizer, Pharmacyclics, Roche; Non-Financial Interests, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO. C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, Servier, MSD, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Principal Investigator: Amgen, Daiichi Sankyo, MSD. R.A. Pazo Cid: Financial Interests, Personal, Advisory Board: Roche, BMS, Servier, Ipsen, Lilly, AstraZeneca; Financial Interests, Personal, Invited Speaker: Servier, BMS, Roche, Eisai; Financial Interests, Personal and Institutional, Local PI, Support for manuscript presentation (funding, provision of study materials, medical writing, article processing charges): Ipsen, Astellas. S. Chandana: Other, Personal, Advisory Board: Daiichi Sankyo, Speakers bureau, Bristol Myers Squibb, Janssen Biotech, Natera; Financial Interests, Institutional, Research Funding: AbbVie, AstraZeneca, Biosplice, Exact Sciences, Ipsen, Johnson & Johnson, Merck, Mirati Therapeutics, QED Therapeutics, TerSera Therapeutics, Zymeworks. A. Dean: Financial Interests, Personal, Other, Travel/accommodation expenses: Novartis; Financial Interests, Personal, Stocks or ownership: A2A Pharmaceuticals; Non-Financial Interests, Personal, Other, Honoraria: Amgen; Non-Financial Interests, Personal, Non remunerated activity: A2A Pharmaceuticals. I. Kiss: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme Oncology; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Merck, Merck Sharp & Dohme Oncology, Laboratoires Pierre Fabre, Servier. T.O. Goetze: Financial Interests, Personal, Advisory Role: Bayer, Bristol Myers Squibb, Foundation Medicine, Incyte, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Roche, Servier; Financial Interests, Personal, Non remunerated activity: Amgen, Bristol Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Roche, Sanofi Aventis, Servier; Financial Interests, Institutional, Research Funding: AstraZeneca, Federal Joint Committee (gBA), German Cancer Aid (Deutsche Krebshilfe), German Research Foundation (DFG), Incyte, Eli Lilly and Company; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly and Company. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. A.S. Paulson: Financial Interests, Personal, Stocks or ownership: Actinium, Alexion Pharmaceuticals, Aptose Biosciences, Lynx Health, Stromatis Pharma; Financial Interests, Personal, Non remunerated activity: Cardinal Health; 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, QED Therapeutics, Stromatis Pharma; Financial Interests, Personal, Speaker’s Bureau: IDEO Oncology; Financial Interests, Institutional, Research 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. 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, GSK, 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, Coordinating PI: Boston Biomedical, Incyte; Financial Interests, Institutional, Steering Committee Member: Seattle Genetics; Non-Financial Interests, Advisory Role: Imugene, Sun Biopharma. S. Pant: Financial Interests, Personal, Advisory Role: 4D Pharma, Ipsen, Janssen, Novartis, Xencor, Zymeworks; Financial Interests, Personal, Non remunerated activity: 4D Pharma; Financial Interests, Institutional, Research Funding: 4D Pharma, Arcus Biosciences, ArQule, Astellas Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Elicio Therapeutics, Five Prime Therapeutics, GSK, Ipsen, Janssen, Eli Lilly and Company, Mirati Therapeutics, NGM Biopharmaceuticals, Novartis, OncoResponse, Purple Biotech, RedHill Biopharma, Rgenix, Sanofi Aventis, Xencor. R. Hubner: Financial Interests, Personal, Advisory Board: BeiGene, Ipsen, Novartis; Financial Interests, Personal, Other, Travel/accommodation expenses: Roche. Z. Xiao: Financial Interests, Personal, Full or part-time Employment: Ipsen; Financial Interests, Personal, Stocks or ownership: Ipsen. L. Zhang: Financial Interests, Personal, Full or part-time Employment: Ipsen. F.M. Benzaghou: Financial Interests, Personal, Full or part-time Employment: Ipsen; Financial Interests, Personal, Stocks or ownership: Ipsen. E.M. O'Reilly: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, BioNTech, Merck, AstraZeneca, Novartis, FibroGen, Astellas, Tempus, Merus, BMS, Berry Genomics, Exelixis, Incyte, Helio, Neogene, Newbridge, QED, 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, Local PI: Genentech/Roche, Arcus, Elicio; Financial Interests, Personal and Institutional, Coordinating PI: BioNTech; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Pertzye; Financial Interests, Institutional, Research Grant: Parker Institute for Cancer Immunotherapy; 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, Other, Editor: American Society of Clinical Oncology, American Association of Cancer Research (AACR); Other, Other, Advisor/no compensation: Thetis, BioSapien. Z.A. Wainberg: Financial Interests, Personal, Advisory Role: Amgen, Arcus Biosciences, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Ipsen, Eli Lilly and Company, Merck, Merck KGaA, Novartis, Pfizer, PureTech Health, QED Therapeutics, Seagen; Financial Interests, Personal, Other, Travel and accommodation expenses: Bayer, Eli Lilly and Company, Merck; Financial Interests, Institutional, Research Funding: Five Prime Therapeutics, Merck, Novartis, Pfizer, Plexxikon. All other authors have declared no conflicts of interest.