Academic Journal
Netupitant versus aprepitant: model-predicted neurokinin-1 receptor occupancy and implications for long-delayed nausea and vomiting prevention.
| Τίτλος: | Netupitant versus aprepitant: model-predicted neurokinin-1 receptor occupancy and implications for long-delayed nausea and vomiting prevention. |
|---|---|
| Συγγραφείς: | Iihara H; Department of Pharmacy, Gifu University Hospital, Gifu, Japan. iihara.hirotoshi.p7@f.gifu-u.ac.jp.; Cancer Center, Gifu University Hospital, Gifu, Japan. iihara.hirotoshi.p7@f.gifu-u.ac.jp., Bianchini G; Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.; School of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy., Aapro M; Genolier Cancer Center, Clinique de Genolier, Genolier, Switzerland., Licata L; Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy., Bernareggi A; Clinical Pharmacology Consultant, Concorezzo, Italy., Navari RM; World Health Organization, Mount Olive, AL, USA., Park YH; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Jordan K; Department of Hematology, Oncology and Palliative Medicine, Ernst Von Bergmann Hospital, Potsdam, Germany.; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Vidal M; Department of Medical Oncology, Hospital Clinic; Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS; Department of Medicine, University of Barcelona, Barcelona, Spain., Scotté F; Interdisciplinary Cancer Course Department, Gustave Roussy Cancer Institute, Villejuif, France., Roeland EJ; Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA., Schwartzberg L; Renown Health-Pennington Cancer Institute, University of Nevada, Reno, NV, USA., Rugo HS; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. |
| Πηγή: | Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer [Support Care Cancer] 2026 Sep 05; Vol. 34 (10). Date of Electronic Publication: 2026 Sep 05. |
| Τύπος έκδοσης: | Journal Article; Comparative Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer International Country of Publication: Germany NLM ID: 9302957 Publication Model: Electronic Cited Medium: Internet ISSN: 1433-7339 (Electronic) Linking ISSN: 09414355 NLM ISO Abbreviation: Support Care Cancer Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin : Springer International, c1993- |
| Ιατρικοί όροι (MeSH): | Vomiting*/prevention & control , Vomiting*/chemically induced , Nausea*/prevention & control , Nausea*/chemically induced , Antiemetics*/pharmacokinetics , Antiemetics*/pharmacology , Antiemetics*/administration & dosage , Antiemetics*/therapeutic use , Morpholines*/pharmacokinetics , Morpholines*/pharmacology , Morpholines*/administration & dosage , Morpholines*/therapeutic use , Neurokinin-1 Receptor Antagonists*/pharmacokinetics , Neurokinin-1 Receptor Antagonists*/pharmacology , Neurokinin-1 Receptor Antagonists*/administration & dosage , Pyridines*/pharmacokinetics , Pyridines*/pharmacology , Pyridines*/administration & dosage , Pyridines*/therapeutic use, Receptors, Neurokinin-1/metabolism ; Antineoplastic Agents/adverse effects ; Aprepitant ; Humans ; Positron-Emission Tomography ; Models, Biological ; Female ; Male ; Time Factors ; Administration, Oral ; Piperazines ; Benzeneacetamides |
| Περίληψη: | Purpose: Nausea and vomiting beyond 5 days after emetogenic chemotherapy or antibody-drug conjugate (ADC) therapy are common, yet the role of neurokinin-1 (NK Methods: Data from previous PK studies were analyzed by compartmental modeling. Positron emission tomography studies assessing striatal NK Results: Model predicted NK Conclusions: Single-dose netupitant maintained NK (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Disclaimer: The authors are fully responsible for all content and editorial decisions for this manuscript. Competing interests: Hirotoshi Iihara: Consulting fees: Astellas Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd.; honoraria for lectures: Astellas Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly and Company., Nippon Kayaku Co., Ltd., Ohara Pharmaceutical Co., Ltd., Sawai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd. Giampaolo Bianchini: Consultancy: Seagen, Roche, AstraZeneca, MSD, Daiichi Sankyo, Menarini, Tethis and Gilead; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Gilead, Seagen, Pfizer, Novartis, Takeda; Support for attending meetings and/or travel: Roche, Pfizer, MSD, Novartis, Daiichi Sankyo, AstraZeneca, Takeda, Gilead, Eli Lilly, Menarini; Advisory Board: Helsinn, Pfizer, Roche, AstraZeneca, Eli Lilly, Novartis, MSD, Daiichi Sankyo, Gilead, Seagen, Menarini, Exact Science. Matti Aapro: Consulting or advisory role: Helsinn Healthcare, Daiichi Sankyo, Pfizer (institution), Novartis (institution), Fresenius Kabi (institution), Lilly (institution); speakers’ bureau: Amgen, Helsinn Healthcare, Novartis, Pfizer, Genomic Health, AstraZeneca, Knight Pharmaceuticals, Immedica; research funding (institution): Helsinn Healthcare, Novartis; uncompensated relationships: International Society for Geriatric Oncology (SIOG), Union for International Cancer Control, European Cancer Organisation, AFSOS, MASCC, SPCC, ALLCAn. Luca Licata: has received consulting fee from Exact Sciences, Helsinn, AstraZeneca, Daiichi Sankyo; honoraria for speakers’ bureaus from Gilead, Exact Sciences, Helsinn, Lilly, AstraZeneca, Daiichi Sankyo; support for attending meetings from Lilly, Gilead, Accord, Helsinn, Roche; has served on Advisory Board for Lilly, Exact Sciences, AstraZeneca, Italfarmaco, Daiichi Sankyo, Accord, Pfizer, Gilead, Novartis. Alberto Bernareggi: Nothing to disclose. Rudolph M. Navari: Nothing to disclose. Yeon Hee Park: Advisory board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Gilead, BMS Jazz Pharm; Principal investigator: AstraZeneca, Pfizer, Roche, Daiichi Sankyo, Novartis, MSD, Gilead, BMS, Jazz Pharm; Funding: AstraZeneca, Pfizer, Roche, MSD, Helsinn; Speaker fees: Roche, Novartis, Helsinn; Accommodation: Helsinn; Other: Daiichi Sankyo. Karin Jordan: Advisory board and/or honoraria for presentations for MSD, Amgen, Roche, Hexal, Esteve, Helsinn, Art-Tempi, Onkowissen, AstraZeneca, Takeda, Mundipharma, med update GmbH, Vifor, Karyopharm, and royalties from Kluwer and Elsevier. María Vidal: Advisory board: AstraZeneca/Daiichi Sankyo, Novartis/Pfizer, Pfizer, Roche; Speaker fees: AstraZeneca/Daiichi Sankyo, Gilead Sciences, Guardant Health, Novartis/Pfizer, Veracyte; Support for attending meetings and/or travel: Pfizer, Gilead Sciences, AstraZeneca/Daiichi Sankyo. Florian Scotté: Consulting or advisory role: Gilead, Sanofi, MSD, GSK, Helsinn, Pharmanovia, Léo Pharma, Amgen, Pierre Fabre Oncologie, Sandoz, La Roche-Posay, Daiichi Sankyo, AstraZeneca, Arrow, Pfizer, BMS, Viatris, Menarini Stemline. research funding (institution): Gilead, AMGEN, Helsinn Healthcare. uncompensated relationships: MASCC, AFSOS, ESMO. Eric J. Roeland: member of the scientific advisory board for Pfizer, Napo Pharmaceuticals, and Aveo Pharmaceuticals; consultant for Dexcel Pharma, and Ryvu Therapeutics; research funding Napo Pharmaceuticals, Pfizer (all to institution); and expert witness for Heron Therapeutics. Lee Schwartzberg: Consultant/advisor: AstraZeneca, Daiichi Sankyo, Helsinn, Novartis, Foundation Medicine, Bristol Myers Squibb. Speaker Bureau: Merck, AstraZeneca, Daiichi Sankyo, Agendia. Hope S. Rugo: Consultancy/advisory fees from Napo, Bristol Myers Squibb, and Helsinn; research support to her former institution (UCSF) from AstraZeneca, Daiichi Sankyo, Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Gilead Sciences, Inc., Lilly; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer, Stemline Therapeutics, and Ambryx. |
| References: | Ballatori E, Roila F, Ruggeri B et al (2007) The impact of chemotherapy-induced nausea and vomiting on health-related quality of life. Support Care Cancer 15:179–185. https://doi.org/10.1007/s00520-006-0109-7. (PMID: 10.1007/s00520-006-0109-716941136) Fernández-Ortega P, Caloto MT, Chirveches E et al (2012) Chemotherapy-induced nausea and vomiting in clinical practice: impact on patients’ quality of life. Support Care Cancer 20:3141–3148. https://doi.org/10.1007/s00520-012-1448-1. (PMID: 10.1007/s00520-012-1448-122460057) National Comprehensive Cancer Network, 2025. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Antiemesis. Version 2.2025. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf . Accessed December 9, 2025. Haiderali A, Menditto L, Good M, Teitelbaum A, Wegner J (2011) Impact on daily functioning and indirect/direct costs associated with chemotherapy-induced nausea and vomiting (CINV) in a U.S. population. Support Care Cancer 19:843–851. https://doi.org/10.1007/s00520-010-0915-9. (PMID: 10.1007/s00520-010-0915-920532923) Chow R, Yin LB, Baqri W et al (2023) Prevalence and predictors of long-delayed (> 120 h) chemotherapy-induced nausea and vomiting (CINV)-a systematic review and individual patient data meta-analysis. Support Care Cancer 31. https://doi.org/10.1007/s00520-023-07978-y. (PMID: 10.1007/s00520-023-07978-y37535218) Jordan K, de Azambuja E, Del Barrio MÁG et al (2025) Going beyond the 2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting. Eur J Cancer 222:115451. https://doi.org/10.1016/j.ejca.2025.115451. (PMID: 10.1016/j.ejca.2025.11545140288116) Navari RM, Nelson WW, Shoaib S, Singh R, Zhang W, Bailey WL (2023) Real-world treatment outcomes, healthcare resource use, and costs associated with antiemetics among cancer patients on cisplatin-based chemotherapy. Adv Ther 40(7):3217–3226. https://doi.org/10.1007/s12325-023-02537-7. Bianchini G, Arpino G, Biganzoli L et al (2022) Emetogenicity of antibody-drug conjugates (ADCs) in solid tumors with a focus on trastuzumab deruxtecan: insights from an Italian expert panel. Cancers (Basel) 14:1022. https://doi.org/10.3390/cancers14041022. Park YH, Bianchini G, Cortés J et al (2025) Nausea and vomiting in an evolving anticancer treatment landscape: long-delayed and emetogenic antibody-drug conjugates. Future Oncol 21:1261–1272. https://doi.org/10.1080/14796694.2025.2479417. (PMID: 10.1080/14796694.2025.24794174010559511988240) Jordan K (2025) Beyond the usual window: persistent nausea with trastuzumab deruxtecan calls for new management strategies. Ann Oncol 36(3):5. https://doi.org/10.1016/j.annonc.2024.10.017. (PMID: 10.1016/j.annonc.2024.10.017) Rugo HS, Tolaney SM, Loirat D et al (2022) Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer 8(1):98. https://doi.org/10.1038/s41523-022-00467-1. (PMID: 10.1038/s41523-022-00467-1360386169424318) Akynzeo® (netupitant and palonosetron) capsules, for oral use; Akynzeo (fosnetupitant and palonosetron) for injection, for intravenous use; Akynzeo (fosnetupitant and palonosetron) injection, for intravenous use [prescribing information]. Helsinn Therapeutics (US), Inc.; 2023. Emend (aprepitant) capsules, for oral use; Emend® (aprepitant) for oral suspension [prescribing information]. Merck Sharp & Dohme Corp.; 2022. Emend (fosaprepitant) for injection [prescribing information]. Merck Sharp & Dohme Corp.; 2022. Bergström M, Hargreaves RJ, Burns HD et al (2004) Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry 55:1007–1012. https://doi.org/10.1016/j.biopsych.2004.02.007. (PMID: 10.1016/j.biopsych.2004.02.00715121485) Emend (aprepitant) capsules. Clinical pharmacology review. NDA 21549/S-025. 2015. https://www.fda.gov/files/drugs/published/207865-Aprepitant-Clinpharm-PREA.pdf . Accessed December 9, 2025. Hesketh PJ, Rossi G, Rizzi G et al (2014) Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized, dose-ranging pivotal study. Ann Oncol 25:1340–1346. https://doi.org/10.1093/annonc/mdu110. (PMID: 10.1093/annonc/mdu110246081964071755) Spinelli S, Calcagnile C, Giuliano C et al (2013) Netupitant PET imaging and ADME studies in humans. J Clin Pharmacol 54:97–108. https://doi.org/10.1002/jcph.198. (PMID: 10.1002/jcph.198241228714282341) Majumdar AK, Howard L, Goldberg MR et al (2006) Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. J Clin Pharmacol 46:291–300. https://doi.org/10.1177/0091270005283467. (PMID: 10.1177/009127000528346716490805) Calcagnile S, Lanzarotti C, Gutacker M, Jakob-Rodamer V, Kammerer KP, Timmer W (2015) Evaluation of the effect of food and age on the pharmacokinetics of oral netupitant and palonosetron in healthy subjects: a randomized, open-label, crossover phase 1 study. Clin Pharmacol Drug Dev 4:377–386. https://doi.org/10.1002/cpdd.192. (PMID: 10.1002/cpdd.19227137147) Caberlotto L, Hurd YL, Murdock P, Wahlin JP, Melotto S, Corsi M, Carletti R (2003) Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain. Eur J Neurosci 17(9):1736–1746. https://doi.org/10.1046/j.1460-9568.2003.02600.x. (PMID: 10.1046/j.1460-9568.2003.02600.x12752772) DrugBank. Netupitant. 2021. https://go.drugbank.com/drugs/DB09048 . Accessed December 9, 2025. DrugBank. Aprepitant. 2025. https://go.drugbank.com/drugs/DB00673 . Accessed December 9, 2025. Huskey S, Dean BJ, Bakhtiar R et al (2003) Brain penetration of aprepitant, a substance P receptor antagonist, in ferrets. Drug Metab Dispos 31:785–791. https://doi.org/10.1124/dmd.31.6.785. (PMID: 10.1124/dmd.31.6.78512756213) Baron-Hay S, Aapro M, Bernareggi A, Schwartzberg L (2019) Timing flexibility of oral NEPA, netupitant-palonosetron combination, administration for the prevention of chemotherapy-induced nausea and vomiting (CINV). Support Care Cancer 27:1309–1317. https://doi.org/10.1007/s00520-019-4640-8. (PMID: 10.1007/s00520-019-4640-8306857936394711) Li S, Kong S, Bernareggi A (2026) Differential NK<sub>1</sub> receptor occupancy profiles of netupitant and rolapitant: a pharmacokinetic/pharmacodynamic modeling analysis. Proceedings of the 29th Annual Meeting of the Chinese Society of Clinical Oncology (CSCO); September 2026; Jinan, China. Abstract 26966. Hata A, Shiraishi Y, Inui N et al (2022) Exploratory analysis comparing fosnetupitant versus fosaprepitant for prevention of highly emetogenic chemotherapy-induced nausea and vomiting (CINV): a randomized, double-blind, phase 3 study (CONSOLE). Oncol Ther 10:253–262. https://doi.org/10.1007/s40487-022-00188-2. (PMID: 10.1007/s40487-022-00188-2352468279098704) Zelek L, Navari R, Aapro M, Scotté F (2023) Single-dose NEPA versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Cancer Med 12:15769–15776. https://doi.org/10.1002/cam4.6121. (PMID: 10.1002/cam4.61213753794310469631) Navari RM, Binder G, Bonizzoni E, Clark-Snow R, Olivari S, Roeland EJ (2021) Single-dose netupitant/palonosetron versus 3-day aprepitant for preventing chemotherapy-induced nausea and vomiting: a pooled analysis. Future Oncol 17:3027–3035. https://doi.org/10.2217/fon-2021-0023. (PMID: 10.2217/fon-2021-002333878896) Navari RM, Inui N, Tyle, T (2024) Individual patient data meta-analysis of NEPA vs. aprepitant antiemetic regimens in the prevention of chemotherapy-induced nausea and vomiting (CINV). Support Care Cancer 32:S434. Akynzeo 300 mg/0.5 mg hard capsules. Akynzeo 235 mg fosnetupitant, corresponding to 197.5 mg netupitant, and 0.25 mg palonosetron powder for concentrate for solution [summary of product characteristics]. Helsinn Birex Pharmaceuticals Ltd.; 2024. |
| Contributed Indexing: | Keywords: Antibody–drug conjugate; Aprepitant; CINV; Nausea; Netupitant; Vomiting |
| Substance Nomenclature: | 1NF15YR6UY (Aprepitant) 0 (Antiemetics) 0 (Morpholines) 0 (Receptors, Neurokinin-1) 7732P08TIR (netupitant) 0 (Neurokinin-1 Receptor Antagonists) 0 (Pyridines) 0 (Antineoplastic Agents) 0 (Piperazines) 0 (Benzeneacetamides) |
| Entry Date(s): | Date Created: 20260905 Date Completed: 20260905 Latest Revision: 20261015 |
| Update Code: | 20261016 |
| PubMed Central ID: | PMC13546154 |
| DOI: | 10.1007/s00520-026-11175-y |
| PMID: | 42701103 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1433-7339 |
|---|---|
| DOI: | 10.1007/s00520-026-11175-y |