Plain Language Summary
What is this summary about?
This is a summary of a clinical study called NAPOLI 3. The NAPOLI 3 study included 770 patients with a type of pancreatic cancer called pancreatic ductal adenocarcinoma(PDAC). All of the patients in NAPOLI 3 had metastatic PDAC (mPDAC), meaning that their cancer had spread from their pancreas to other parts of the body. None of the patients had received any previous treatment for metastatic cancer, meaning that they had untreated mPDAC. In NAPOLI 3, the study team wanted to compare a new combination chemotherapy called NALIRIFOX with another chemotherapy combination called GemNabPac in patients with untreated mPDAC. NALIRIFOX includes four chemotherapy drugs: liposomal irinotecan, oxaliplatin, leucovorin and fluorouracil.GemNabPac includes two chemotherapy drugs: nab-paclitaxel and gemcitabine. GemNabPac is a treatment that is already used by doctors and is approved by regulatory agencies in the USA and Europe for patients with untreated mPDAC. This study looked at the survival time of patients, the time for the cancer to worsen after treatment and the side effects of both chemotherapy combinations.
What were the results?
The study showed that NALIRIFOX increased survival time and the length of time it took for the cancer to worsen compared with GemNabPac. The number and severity of side effects was similar between the two treatments, but the type of side effects differed between the two treatments. Severe side effects that affect the blood were less common with NALIRIFOX than GemNabPac, whereas severe digestive side effects were more common with NALIRIFOX than GemNabPac. There were no new safety concerns for either of the combinations.
What do the results mean?
NAPOLI 3 is the first study to compare two different combination chemotherapy treatments in patients with untreated mPDAC. The results of NAPOLI 3 mean that NALIRIFOX is a possible treatment option for patients diagnosed with mPDAC. In early 2024, NALIRIFOX was approved by the regulatory agency in the USA (called the US Food and Drug Administration or FDA) and by the regulatory agency in Europe (called the European Medicines Agency or EMA) because of the results of NAPOLI 3. NALIRIFOX is now approved for patients with untreated mPDAC in the USA, Europe (European Union countries and Switzerland), Taiwan, Australia and Egypt, and is the first new treatment approved for people with untreated mPDAC since 2013.
This is an abstract of the Plain Language Summary of Publication article.
View the full Plain Language Summary PDF of this article to read the full-text
Acknowledgments
The authors of this article thank the patients who participated in this study and their families, as well as the investigators, co-investigators and staff at each of the clinical sites.
Disclosure statement
ZAW has received grants or contracts from Arcus and Bristol Myers Squibb, consulting fees from Amgen, Arcus, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb,Daiichi Sankyo, Gilead, Ipsen, Merck Sharp & Dohme and Seagen, support for attending meetings or travel from Amgen, Bayer and Merck Sharp & Dohme, and has participated on a data safety monitoring board or advisory board for Mirati and Pfizer. DM has received grants or contracts from Celgene, Evotec, Incyte, iOnctura,Roche and Servier, consultancy fees from Incyte, iOnctura, IQVIA, Merck Sharp & Dohme, Servier and Taiho Pharmaceutical, and has participated on a data safety monitoring board or advisory board for Incyte, Servier, Taiho Pharmaceutical and Terumo. TM has received grants or contracts (personal) from Merck Sharp & Dohme, Novocure, QED Therapeutics, Roche, Sanofi-Aventis, Servier and Zymeworks, and received grants or contracts to their institution from AbbVie Farmaceútica,Ability Pharmaceuticals, Agios Pharmaceuticals, Amgen, Aslan Pharmaceuticals, AstraZeneca, Basilea Pharmaceutica International, Bayer, BeiGene, BioKeralty Research Institute, BioLineRx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb, Cantargia, Celgene, Eisai, Eli Lilly and Company, Erytech Pharma,FibroGen, Halozyme, Incyte, Ipsen, Loxo Oncology, MedImmune, Merck Sharp & Dohme, Nelum, Novartis, Novocure, OncoMed Pharmaceuticals, QED Therapeutics,Roche, VCN Biosciences and Zymeworks, payment or honoraria from Janssen and Lilly, support for attending meetings or travel from AstraZeneca, Incyte, Merck Sharp & Dohme, Sanofi and Servier, and has participated on a data safety monitoring board or advisory board for Ability Pharmaceuticals, AstraZeneca, Basilea Pharma, Baxter, BioLineRX, Celgene, Eisai, Incyte and Ipsen. RPC has received consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly and Company, Ipsen, Servier and Roche, honoraria from Astellas, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Roche and Servier, payment or honoraria from Astellas, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Roche and Servier, and support for attending meetings or travel from Bristol Myers Squibb,Eli Lilly and Company, Roche and Servier. SRC has received grants or contracts from AstraZeneca, Exact Sciences, Merck Sharp & Dohme, QED Therapeutics, TerSera Therapeutics, and Zymeworks (personal) and Ipsen (institution), payment or honoraria from Bristol Myers Squibb, Janssen and Natra (speaker’s bureau), and has participated on a data safety monitoring board or advisory board for Daiichi Sankyo. CDLF has received consultancy fees from Bristol Myers Squibb, Daiichi Sankyo,Eisai, Ipsen, Merck Sharp & Dohme, Pierre Fabre Oncologie and Roche, and support for attending meetings or travel from Merck Sharp & Dohme, Pierre Fabre Oncologie and Roche. AD has received support for attending meetings or travel from Juniper Biologics. TOG has received grants or contracts from German Research Foundation and Incyte, consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Deciphera, Eli Lilly and Company, Foundation Medicine, MCI, Merck Sharp & Dohme, Novartis, Roche, Sanofi Aventis and Servier, payment or honoraria from Amgen, Bristol Myers Squibb,Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Roche, Sanofi Aventis and Servier, has received payment for an expert testimony for Bundesinstitut für Arzneimittel und Medizinprodukte and Daiichi Sankyo, participated on a data safety monitoring board or advisory board for Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, Foundation Medicine, MCI, Merck Sharp & Dohme, Novartis, Roche, Sanofi Aventis and Servier, and has had a leadership or fiduciary role in board, society, committee or advocacy group with Arbeitgemeinschaft Internistische Onkologie. EVC has received grants or contracts from Amgen, Bayer,Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Ipsen, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche and Servier, and consulting fees from AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline,Incyte, Ipsen, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre Oncologie, Pfizer, Roche, Seagen, Servier, Takeda, Terumo, Taiho Pharmaceutical and Zymeworks. ASP has received research funding (personal) from Buzzard Pharmaceuticals, and research funding (institution) from AstraZeneca, Bayer, BioNTech,Bristol Myers Squibb, Camurus, Deciphera, Eli Lilly and Company, Exelixis, G1 Therapeutics, Gilead Sciences, Gritstone Bio, Hutchinson MediPharma, Incyte, Innovative Cellular Therapeutics, Inspirna, Ipsen, ITM Oncologics, Merck Sharp & Dohme, Novartis, NuCana, Relay Therapeutics, Regenxbio, Seagen, SOTIO Biotech, Taiho Pharmaceutical, Tempus, TransThera Biosciences and Zentalis Pharmaceuticals, had a consulting or advisory role at AADI Bioscience, Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, Hutchison MediPharma, Incyte, Ipsen, Eli Lilly and Company, Mirati Therapeutics, Novartis, Pfizer, QED Therapeutics, Servier and Stromatis Pharma, received payment or honoraria from Cardinal Health (honoraria), Ideo Oncology(speaker’s bureau), received support for attending meetings or travel from AADI Bioscience, Camurus, Mirati Therapeutics, NuCana and Pfizer, and has stock or stock options in Actinium, Alexion Pharmaceuticals, Aptose Biosciences and Lynx Health. TB-S has received research funding (institution) from Agios, Arcus, Arys, Atreca,Bayer, Boston Biomedical, Bristol Myers Squibb Eisai, Celgene, Eli Lilly and Company, Ipsen, Clovis, Seagen, Genentech, Novartis, Mirati Therapeutics, Merus,Abgenomics, Incyte and Pfizer, received royalties from UpToDate, received consultancy fees from Stemline, AbbVie, Aptitude Health, AstraZeneca, Beigene, Blueprint Medicines, Boehringer Ingelheim, Caladrius Biosciences, Celularity, Daiichi Sankyo, Deciphera, Exact Science, Exelixis, Foundation Medicine, GlaxoSmithKline,Illumina, Janssen, Kanaph, MJH Life Sciences, Natera, Sanofi, Sobi, Treos Bio and Zai Labs (personal), and Arcus, Bayer, Eisai, Genentech, Incyte, Ipsen, Merck Sharp & Dohme, Merck KGaA, Merus, Pfizer, Seagen and Servier (institution), received patents WO/2018/183488 and WO/2019/055687, and has participated on a data safety monitoring board or advisory board for 1Globe, AstraZeneca, Artiva, Eisai, Exelixis, Fibrogen, Immuneering, Imugene, Merck, PanCan, Replimune, Sun Biopharma,Suzhou Kintor, The Valley Hospital and Xilis. SP has participated on a data safety monitoring board or advisory board for Askgene Pharma, Boehringer Ingelheim,Ipsen, Janssen, Novartis and Zymeworks. RAH has received honoraria from Eisai, and participated on a data safety monitoring board or advisory board for Beigene and Ipsen. ZX, HC and FB are employed at Ipsen and have stock or stock options in Ipsen. EMO has received grants or contracts from AstraZeneca, Arcus, BioNTech,Elicio, Genentech/Roche, NIH/NCI, Parker Institute and Pertzye, consulting fees from AstraZeneca, Astellas, Autem, BioNTech, BioSapien, Boehringer Ingelheim,Bristol Myers Squibb, Fibrogen, Ipsen, Merck Sharp & Dohme, Merus, Neogene, Novartis, Novocure, Revolution Medicines, Tempus and Thetis (personal), Agios, Eisai and Genentech/Roche (spouse), has had an uncompensated leadership or fiduciary role in board, society, committee or advocacy groups with Avner Foundation,National Pancreas Foundation and Pancreas Cancer Action Network, and has received other financial or non-financial interests from American Association of Cancer Research and American Society of Clinical Oncology. IK and WJL declare no competing interests. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Writing support for this summary was provided by Amber Tear and Emma Bolton of Oxford PharmaGenesis and funded by Ipsen.
Patient reviewers on this PLSP have received an honorarium from Future Oncology for their review work but have no other relevant financial relationships to disclose.
Funding
This manuscript was funded by Ipsen. The funder was involved in study design, data collection and analysis, decision to publish and preparation of the manuscript.