{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:02:26Z","timestamp":1791133346066,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008130","name":"Helsinn Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although control of chemotherapy\u2010induced nausea and vomiting (CINV) is substantially improved with guideline\u2010directed antiemetic prophylaxis, breakthrough CINV remains a significant clinical patient problem. In subsequent cycles after breakthrough occurs, antiemetic guidelines recommend adding agents not used in the initial cycle. This study was designed to evaluate the use of NEPA (netupitant\/palonosetron) plus dexamethasone with or without olanzapine for the prevention of CINV in the second cycle of chemotherapy for patients receiving highly (HEC) or moderately emetogenic chemotherapy (MEC) who developed breakthrough CINV in their first cycle despite guideline\u2010directed prophylactic antiemetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a Phase 2, single center, open\u2010label study. Patients received guideline\u2010recommended prophylactic antiemetics in Cycle 1 based on the chemotherapy emetogenicity. Patients who experienced breakthrough CINV in Cycle 1 received intravenous (IV) NEPA (Day 1) plus dexamethasone (Days 1\u20134) and olanzapine (Days 1\u20134) for HEC or IV NEPA (Day 1) plus dexamethasone (Days 1\u20134) for MEC in Cycle 2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 227 patients enrolled in Cycle 1, 100 patients (<jats:italic>n<\/jats:italic>\u2009=\u200937 HEC, 63 MEC) experienced breakthrough CINV and received the NEPA\u2010based treatments in Cycle 2. The complete response (no emesis\/no rescue use) rates [95% confidence intervals] during the overall (0\u2013120\u2009h) phase were 76% [59%, 88%] and 79% [67%, 89%] in the HEC and MEC groups, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results show that NEPA with or without olanzapine is an effective approach for CINV prevention for patients receiving HEC or MEC who develop breakthrough CINV after their first course of chemotherapy. The results support the antiemetic guideline recommendations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link> identifier: NCT06065722<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70549","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T04:20:36Z","timestamp":1743308436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["NEPA <scp>(<\/scp>Netupitant\/Palonosetron) for the Prevention of Chemotherapy\u2010Induced Nausea and Vomiting (<scp>CINV<\/scp>) in Patients Receiving Highly or Moderately Emetogenic Chemotherapy Who Experienced Breakthrough <scp>CINV<\/scp> in Cycle 1 of Chemotherapy: A Phase <scp>II<\/scp> Clinical Trial"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8513-896X","authenticated-orcid":false,"given":"Rudolph M.","family":"Navari","sequence":"first","affiliation":[{"name":"World Health Organization  Mount Olive Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erminio","family":"Bonizzoni","sequence":"additional","affiliation":[{"name":"RIDE2Med Foundation  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1515442"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13620"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2013.06.012"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.10.74"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2013.799141"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S158570"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2018-0577"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.08.048"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-28-131"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suponc.2011.05.002"},{"issue":"14","key":"e_1_2_11_12_1","first-page":"1396","article-title":"Olanzapine for Chemotherapy\u2010Induced Nausea and Vomiting","volume":"375","author":"Navari R. 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