{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:13:32Z","timestamp":1792782812171,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Helsinn Healthcare SA"},{"name":"Gifu University","id":[{"id":"https:\/\/ror.org\/024exxj48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Support Care Cancer"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Nausea and vomiting beyond 5\u00a0days after emetogenic chemotherapy or antibody\u2013drug conjugate (ADC) therapy are common, yet the role of neurokinin-1 (NK\n                      <jats:sub>1<\/jats:sub>\n                      ) receptor antagonists in this setting remains underrecognized. We used pharmacokinetic\/pharmacodynamic (PK\/PD) modeling to estimate the NK\n                      <jats:sub>1<\/jats:sub>\n                      receptor occupancy (RO), a proxy for clinical efficacy, for up to 20\u00a0days after a single 300\u00a0mg dose of oral netupitant, 3-day oral aprepitant (125\u00a0mg on day 1; 80\u00a0mg on days 2\u20133), or a single 165\u00a0mg dose of oral aprepitant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from previous PK studies were analyzed by compartmental modeling. Positron emission tomography studies assessing striatal NK\n                      <jats:sub>1<\/jats:sub>\n                      RO were used to develop maximum drug effect PD models, which were fitted to NK\n                      <jats:sub>1<\/jats:sub>\n                      RO data as a function of plasma concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Model predicted NK\n                      <jats:sub>1<\/jats:sub>\n                      RO exceeded 90% at 3\u00a0h for all treatments. Thereafter, RO declined more gradually with netupitant (76%, 70%, 60%, and 21% on days 5, 7, 10, and 20, respectively) than with 3-day aprepitant (81%, 39%, 3%, and negligible) or single-dose aprepitant (45%, 10%, &lt;\u20091%, and negligible). The half-life of netupitant was ~\u20096.1 times longer than aprepitant\u2019s. Netupitant plasma concentration remained above the effective concentration for 50% NK\n                      <jats:sub>1<\/jats:sub>\n                      RO (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) through day 10, whereas aprepitant concentrations fell below the EC\n                      <jats:sub>50<\/jats:sub>\n                      by ~\u2009days 7 and 5 after repeated and single dosing, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Single-dose netupitant maintained NK\n                      <jats:sub>1<\/jats:sub>\n                      RO substantially longer than repeated- and single-dose aprepitant, suggesting greater potential for prolonged prevention of nausea and vomiting in ADC-treated patients. Prospective clinical validation of these model predictions would be beneficial.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00520-026-11175-y","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:11:59Z","timestamp":1788621119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Netupitant versus aprepitant: model-predicted neurokinin-1 receptor occupancy and implications for long-delayed nausea and vomiting prevention"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-454X","authenticated-orcid":false,"given":"Hirotoshi","family":"Iihara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Bianchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Aapro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Licata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Bernareggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph M.","family":"Navari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Hee","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Scott\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Roeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Schwartzberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope S.","family":"Rugo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"11175_CR1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00520-006-0109-7","volume":"15","author":"E Ballatori","year":"2007","unstructured":"Ballatori E, Roila F, Ruggeri B et al (2007) The impact of chemotherapy-induced nausea and vomiting on health-related quality of life. 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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\u2019 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\u2019 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. Mar\u00eda 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 Scott\u00e9: Consulting or advisory role: Gilead, Sanofi, MSD, GSK, Helsinn, Pharmanovia, L\u00e9o 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.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"933"}}