{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T14:40:21Z","timestamp":1786804821992,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":722,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>NEPA, a combination antiemetic of a neurokinin-1 (NK1) receptor antagonist (RA) (netupitant [oral]\/fosnetupitant [intravenous; IV]) and 5-HT3RA, palonosetron] offers 5-day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion-site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK1RAs, particularly fosaprepitant in patients receiving anthracycline-cyclophosphamide (AC)-based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>This phase IIIb, multinational, randomized, double-blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30-minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment-related AEs in both groups. There were no treatment-related injection-site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis\/no rescue) rates observed in cycle 1 (overall [0\u2013120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>IV NEPA was highly effective and safe with no associated hypersensitivity and injection-site reactions in patients receiving AC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2019-0527","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T19:25:14Z","timestamp":1575487514000},"page":"e589-e597","source":"Crossref","is-referenced-by-count":31,"title":["Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy"],"prefix":"10.1093","volume":"25","author":[{"given":"Lee","family":"Schwartzberg","sequence":"first","affiliation":[{"name":"Hematology & Oncology, West Cancer Center, Germantown, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph","family":"Navari","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Clark-Snow","sequence":"additional","affiliation":[{"name":"Overland Park, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterine","family":"Arkania","sequence":"additional","affiliation":[{"name":"The Institute of Clinical Oncology, Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Radyukova","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy, Clinical Oncology Center, Omsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Patel","sequence":"additional","affiliation":[{"name":"CARTI Cancer Center, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Voisin","sequence":"additional","affiliation":[{"name":"Helsinn Healthcare, Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Helsinn Healthcare, Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Wickham","sequence":"additional","affiliation":[{"name":"Rapid River, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Gralla","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Albert Einstein College of Medicine, Bronx, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Aapro","sequence":"additional","affiliation":[{"name":"Cancer Centre, Clinique de Genolier, Genolier, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Roeland","sequence":"additional","affiliation":[{"name":"Oncology & Palliative Care, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,8]]},"reference":[{"key":"2021122510230033400_R1","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1200\/JCO.2017.74.4789","article-title":"Antiemetics: American Society of Clinical Oncology Clinical practice guideline update","volume":"35","author":"Hesketh","year":"2017","journal-title":"J Clin Oncol"},{"issue":"suppl 5","key":"2021122510230033400_R2","doi-asserted-by":"crossref","first-page":"v119","DOI":"10.1093\/annonc\/mdw270","article-title":"2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients","volume":"27","author":"Roila","year":"2016","journal-title":"Ann Oncol."},{"key":"2021122510230033400_R3","doi-asserted-by":"crossref","first-page":"883","DOI":"10.6004\/jnccn.2017.0117","article-title":"NCCN guidelines insights: Antiemesis, Version 2.2017","volume":"15","author":"Berger","year":"2017","journal-title":"J Natl Compr Canc Netw"},{"key":"2021122510230033400_R4","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1093\/annonc\/mds021","article-title":"The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): The Pan European Emesis Registry (PEER)","volume":"23","author":"Aapro","year":"2012","journal-title":"Ann Oncol"},{"key":"2021122510230033400_R5","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1200\/JOP.2012.000816","article-title":"Antiemetic guideline consistency and incidence of chemotherapy-induced nausea and vomiting in US community oncology practice: INSPIRE study","volume":"10","author":"Gilmore","year":"2014","journal-title":"J Oncol Pract"},{"key":"2021122510230033400_R6","doi-asserted-by":"crossref","first-page":"294","DOI":"10.6004\/jnccn.2017.7043","article-title":"Ten year trends in antiemetic prescribing in cancer patients receiving highly emetogenic chemotherapy (HEC)","volume":"16","author":"O'Sullivan","year":"2018","journal-title":"J Natl Compr Canc Netw"},{"issue":"suppl","key":"2021122510230033400_R7","first-page":"AB2018","article-title":"Gaps in compliance with current antiemetic guidelines for highly emetogenic chemotherapy","volume":"16","author":"Roeland","year":"2018","journal-title":"J Natl Compr Canc Netw"},{"key":"2021122510230033400_R8","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00520-017-3866-6","article-title":"Chemotherapy-induced nausea and vomiting (CINV) and adherence to antiemetic guidelines: Results of a survey of oncology nurses","volume":"26","author":"Clark-Snow","year":"2019","journal-title":"Support Care Cancer"},{"key":"2021122510230033400_R9","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1007\/s00520-019-04697-1","article-title":"Evaluation of antiemetic practices for prevention of chemotherapy-induced nausea and vomiting: Results of a European Oncology nurse survey","volume":"27","author":"Dielesenger","year":"2019","journal-title":"Support Care Cancer"},{"key":"2021122510230033400_R10","doi-asserted-by":"crossref","DOI":"10.6004\/jnccn.2018.7192","article-title":"Avoidable acute care use associated with nausea and vomiting among patients receiving highly emetogenic chemotherapy or oxaliplatin","volume":"17","author":"Roeland","year":"2019","journal-title":"J Natl Compr Canc Netw"},{"key":"2021122510230033400_R11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejphar.2013.08.049","article-title":"Molecular mechanisms of 5-HT(3) and NK(1) receptor antagonists in prevention of emesis","volume":"722","author":"Rojas","year":"2014","journal-title":"Eur J Pharmacol"},{"key":"2021122510230033400_R12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2012.05.037","article-title":"Inhibition of substance P-mediated responses in NG108-15 cells by netupitant and palonosetron exhibit synergistic effects","volume":"689","author":"Stathis","year":"2012","journal-title":"Eur J Pharmacol"},{"key":"2021122510230033400_R13","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1093\/annonc\/mdu110","article-title":"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","volume":"25","author":"Hesketh","year":"2014","journal-title":"Ann Oncol"},{"key":"2021122510230033400_R14","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/annonc\/mdu101","article-title":"A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy","volume":"25","author":"Aapro","year":"2014","journal-title":"Ann Oncol"},{"key":"2021122510230033400_R15","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1634\/theoncologist.2015-0301","article-title":"Safety of an oral fixed combination of netupitant and palonosetron (NEPA): Pooled data from the phase II\/III clinical program","volume":"21","author":"Aapro","year":"2016","journal-title":"The Oncologist"},{"key":"2021122510230033400_R16","volume-title":"U.S. Prescribing information","author":"Akynzeo (netupitant and palonosetron) capsules; Akynzeo (fosnetupitant and palonosetron) for injection","year":"2018"},{"key":"2021122510230033400_R17","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/annonc\/mdy169","article-title":"Phase III safety study of intravenous NEPA: A novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy","volume":"29","author":"Schwartzberg","year":"2018","journal-title":"Ann Oncol"},{"key":"2021122510230033400_R18","volume-title":"US Prescribing Information","author":"Emend (fosaprepitant) for injection, for intravenous use","year":"2017"},{"key":"2021122510230033400_R19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00520-014-2326-9","article-title":"An analysis of fosaprepitant-induced venous toxicity in patients receiving highly emetogenic chemotherapy","volume":"23","author":"Hegerova","year":"2015","journal-title":"Support Care Cancer"},{"key":"2021122510230033400_R20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.3892\/mco.2016.769","article-title":"Infusion site adverse events in breast cancer patients receiving highly emetic chemotherapy with prophylactic anti-emetic treatment with aprepitant and fosaprepitant: A retrospective comparison","volume":"4","author":"Tsuda","year":"2016","journal-title":"Mol Clin Oncol"},{"key":"2021122510230033400_R21","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s00520-013-2089-8","article-title":"Fosaprepitant induced phlebitis: A focus on patients receiving doxorubicin\/cyclophosphamide therapy","volume":"22","author":"Leal","year":"2014","journal-title":"Support Care Cancer"},{"key":"2021122510230033400_R22","doi-asserted-by":"crossref","first-page":"390","DOI":"10.7150\/jca.7706","article-title":"Highly frequent and enhanced injection site reaction induced by peripheral venous injection of fosaprepitant in anthracycline-treated patients","volume":"5","author":"Sato","year":"2014","journal-title":"J Cancer"},{"key":"2021122510230033400_R23","first-page":"379","article-title":"Differential impact of fosaprepitant on infusion site adverse events between cisplatin- and anthracycline-based chemotherapy regimens","volume":"35","author":"Fujii","year":"2015","journal-title":"Anticancer Res"},{"key":"2021122510230033400_R24","volume-title":"US prescribing information","author":"Cinvanti (aprepitant) injectable emulsion","year":"2018"},{"key":"2021122510230033400_R25","doi-asserted-by":"crossref","first-page":"865","DOI":"10.2217\/fon-2018-0809","article-title":"HTX-019 via 2-min injection or 30-min infusion in healthy subjects","volume":"15","author":"Ottoboni","year":"2019","journal-title":"Future Oncol"},{"key":"2021122510230033400_R26","volume-title":"US Prescribing Information","author":"Varubi (rolapitant) injectable emulsion, for intravenous use","year":"2018"},{"key":"2021122510230033400_R27","author":"U.S. Food & Drug Administration"},{"key":"2021122510230033400_R28","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/BF00434947","article-title":"Quality of life consequences of chemotherapy-induced emesis","volume":"1","author":"Lindley","year":"1992","journal-title":"Qual Life Res"},{"key":"2021122510230033400_R29","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1007\/s00520-003-0482-4","article-title":"Assessing the impact of chemotherapy induced nausea and vomiting on patients'daily lives: A modified version of the Functional Living Index-Emesis (FLIE) with 5-day recall","volume":"11","author":"Martin","year":"2003","journal-title":"Support Care Cancer"},{"key":"2021122510230033400_R30","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.2165\/00003495-200161110-00003","article-title":"Anti-emetics for cancer chemotherapy-induced emesis: Potential of alternative delivery systems","volume":"61","author":"Kraut","year":"2001","journal-title":"Drugs"},{"key":"2021122510230033400_R31","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s12325-018-0707-z","article-title":"Safety of polysorbate 80 in the oncology setting","volume":"35","author":"Schwartzberg","year":"2018","journal-title":"Adv Ther"},{"key":"2021122510230033400_R32","doi-asserted-by":"crossref","first-page":"6459","DOI":"10.2147\/OTT.S158570","article-title":"Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting","volume":"11","author":"Navari","year":"2018","journal-title":"Onco Targets Ther"},{"key":"2021122510230033400_R33","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/jcph.966","article-title":"Bioequivalence of intravenous and oral rolapitant: results from a randomized, open-label pivotal study","volume":"57","author":"Wang","year":"2017","journal-title":"J Clin Pharmacol"},{"key":"2021122510230033400_R34","doi-asserted-by":"crossref","first-page":"429","DOI":"10.2147\/DDDT.S155875","article-title":"Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects: A phase I, open-label, randomized, two-way crossover evaluation","volume":"12","author":"Ottoboni","year":"2018","journal-title":"Drug Des Devel Ther"},{"key":"2021122510230033400_R35","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1093\/annonc\/mdu096","article-title":"A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy","volume":"25","author":"Gralla","year":"2014","journal-title":"Ann Oncol"},{"key":"2021122510230033400_R36","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1517\/14740338.2016.1135899","article-title":"The safety of antiemetic medications for the prevention of chemotherapy-induced nausea and vomiting","volume":"15","author":"Navari","year":"2016","journal-title":"Expert Opin Drug Saf"},{"key":"2021122510230033400_R37","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00520-016-3502-x","article-title":"NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: Results of a randomized, double-blind, phase 3 trial versus oral palonosetron","volume":"25","author":"Aapro","year":"2017","journal-title":"Support Care Cancer"},{"key":"2021122510230033400_R38","author":"The Centers for Medicare & Medicaid Services"},{"key":"2021122510230033400_R39","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1200\/JCO.2005.09.050","article-title":"Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy","volume":"23","author":"Warr","year":"2005","journal-title":"J Clin Oncol"},{"key":"2021122510230033400_R40","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2147\/CMAR.S129059","article-title":"APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide-based highly emetogenic chemotherapy regimens: A post hoc subgroup analysis of the phase III randomized MAGIC trial","volume":"19","author":"Schnadig","year":"2017","journal-title":"Cancer Manag Res"},{"key":"2021122510230033400_R41","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/S1470-2045(15)00034-0","article-title":"Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: A randomised, active-controlled, double-blind, phase 3 trial","volume":"16","author":"Schwartzberg","year":"2015","journal-title":"Lancet Oncol"},{"key":"2021122510230033400_R42","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.2217\/cer-2018-0089","article-title":"Real-world efficacy: Intravenous palonosetron three-drug regimen for chemotherapy-induced nausea and vomiting with highly emetogenic chemotherapy","volume":"7","author":"Schwartzberg","year":"2018","journal-title":"J Comp Eff Res"},{"key":"2021122510230033400_R43","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1186\/2193-1801-3-389","article-title":"Effects of combined netupitant and palonosetron (NEPA), a cancer supportive care antiemetic, on the ECG of healthy subjects: An ICH E14 thorough QT trial","volume":"3","author":"Spinelli","year":"2014","journal-title":"Springerplus."},{"key":"2021122510230033400_R44","doi-asserted-by":"crossref","first-page":"4821a","DOI":"10.1182\/blood.V124.21.4821.4821","article-title":"Cardiac safety of NEPA, a fixed-dose antiemetic combination, administered prior to anthracycline-based chemotherapy","volume":"124","author":"Karthaus","year":"2014","journal-title":"Blood"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2019-0527","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2019-0527","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/25\/3\/e589\/41919148\/oncolo_25_3_e589.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/25\/3\/e589\/41919148\/oncolo_25_3_e589.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T10:23:51Z","timestamp":1640427831000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/25\/3\/e589\/6443642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,8]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,12,8]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2019-0527","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3,1]]},"published":{"date-parts":[[2019,12,8]]}}}