[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-352918-105":59,"doc-detail-352918-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","potential-risk-of-neoplasms-with-fezolinetant-clinical-evidence-mechanisms-and-post-marketing-implications","Potential risk of neoplasms with fezolinetant - clinical evidence, mechanisms, and post-marketing implications","","Fezolinetant was approved in 2023 by the FDA and EMA for moderate to severe menopausal vasomotor symptoms (VMS) as a first-in-class neurokinin 3 receptor (NK3R) antagonist. Although SKYLIGHT and MOONLIGHT supported efficacy and safety, emerging meta- and pooled analyses indicate a significant increase in risk for nonbenign neoplasms. Mechanistic concerns are discussed, including reduced kisspeptin antimetastasis signaling and potential compensatory NK1R activation linked to tumor progression. The review synthesizes clinical, regulatory, and pharmacological evidence and outlines key needs for long-term safety evaluation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/potential-risk-of-neoplasms-with-fezolinetant-clinical-evidence-mechanisms-and-post-marketing-implications/352918/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/potential-risk-of-neoplasms-with-fezolinetant-clinical-evidence-mechanisms-and-post-marketing-implications/352918.png","ImageObject",300,407,{"name":92,"@type":93},"Nguyễn Văn Học","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What drug and condition are discussed in the review?","Question",{"text":112,"@type":113},"The review focuses on fezolinetant, an NK3R antagonist, for treating moderate to severe menopausal vasomotor symptoms (VMS).","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What safety concern is highlighted after approval?",{"text":117,"@type":113},"Across regulatory evaluations and emerging analyses, there is concern about an increased risk of nonbenign neoplasms, based on observed numerical imbalance versus placebo.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanisms are proposed to explain the possible neoplastic risk?",{"text":121,"@type":113},"The review discusses reduced kisspeptin secretion, which may affect antimetastasis functions, and possible compensatory activation of neurokinin 1 receptor (NK1R), implicated in tumor proliferation and metastasis.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},352918,1790156190,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},1374402739827,"https://ap-avatar.wpscdn.com/avatar/14000c97e7351f1a627?x-image-process=image/resize,m_fixed,w_180,h_180&k=1787885694763230660","Potential risk of neoplasms with fezolinetant: clinical evidence, mechanisms, and post-marketing implications  \nEmma Boretti  1, Jean-Michel Dogné  1, and Jonathan Douxfils  1,2  \n1Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences (NARILIS), Faculty of Medicine, University of Namur, Namur 5000, Belgium  \n2 Department of Biological Hematology, CHU Clermont-Ferrand, Hôpital Estaing, Clermont-Ferrand 63100, France  \nCorrespondence: Jonathan Douxfils, PhD, PharmD, Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences (NARILIS), Faculty of Medicine, University of Namur, Rue de Bruxelles, Namur 61-5000, Belgium; Department of Biological Hematology, CHU ClermontFerrand, Hôpital Estaing, Clermont-Ferrand 63100, [France. Email:](France. Email: jonathan.douxfils@unamur.be)[ jonathan.douxfils@unamur.be](France. Email: jonathan.douxfils@unamur.be).  \nAbstract  \nIn 2023, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved fezolinetant (Veozah® in the United States, Veoza® in Europe), a novel neurokinin 3 receptor (NK3R) antagonist and first-in-class nonhormonal drug for treating moderate to severe menopausal vasomotor symptoms (VMS). While its efficacy and safety have been demonstrated through the SKYLIGHT and MOONLIGHT programs, concerns were highlighted regarding a potential increased risk of neoplasms. Although regulatory agencies initially dismissed that risk, emerging data from meta-analysis and pooled analysis consistently showed a significant increase in the risk of nonbenign neoplasms. These findings raise important questions regarding a potential causal link between NK3R antagonists and cancer. By blocking NK3R, fezolinetant can reduce kisspeptin secretion, a ubiquitous peptide known for its antimetastasis function. Furthermore, NK3R blockade may induce compensatory activation of the neurokinin 1 receptor (NK1R), which has been implicated in tumor proliferation, angiogenesis, and metastasis. Because of these mechanistic concerns, long-term safety studies and investigations on the NK3R pathway are essential to clarify the neoplastic risk profile of fezolinetant. This review is based on a PubMed/ MEDLINE search using specific keywords, complemented by screening of regulatory documents and citation tracking.  \nKey Words fezolinetant, menopause, neoplasms, neurokinin-3, hot flashes  \nFezolinetant is a first-in-class neurokinin 3 receptor (NK3R) antagonist recently approved for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. While its clinical efficacy has been demonstrated in large-scale phase-3 trials, an unexpected numerical imbalance in the incidence of neoplasms has emerged across both United States and European regulatory evaluations. Despite these signals, neither the Food and Drug Administration (FDA) nor the European Medicines Agency (EMA) has required specific postauthorization safety (PASS) studies or risk minimization strategies to address this risk. This is concerning, given its novel mechanism and lack of long-term safety data for NK3R antagonists. Additionally, emerging evidence from pharmacological studies suggests plausible indirect mechanisms through which NK3R blockade could interfere with tumor-suppressive pathways, including kisspeptin signaling and immune surveillance.  \nThis manuscript reviews clinical, regulatory, and pharmacological data surrounding fezolinetant safety profile, explores the biological plausibility of a neoplastic risk, and proposes recommendations to enhance its safe use in clinical practice based on a specific PubMed/MEDLINE search using specific keywords,  \ncomplemented by screening of regulatory documents and citation tracking. Both preclinical and clinical studies were reviewed to assess mechanistic plausibility and evaluate the consistency of reported safety signals.  \nRegulatory review Overview  \nOn May 12, 2023, the FDA approved","cbCaifVnEl7neIjl","https://ap.wps.com/l/cbCaifVnEl7neIjl","pdf",519875,12,"English","# Abstract\n# Key Words\n# Regulatory review Overview\n## FDA approval and review imbalance\n## EMA opinion and SKYLIGHT program","[{\"question\":\"What drug and condition are discussed in the review?\",\"answer\":\"The review focuses on fezolinetant, an NK3R antagonist, for treating moderate to severe menopausal vasomotor symptoms (VMS).\"},{\"question\":\"What safety concern is highlighted after approval?\",\"answer\":\"Across regulatory evaluations and emerging analyses, there is concern about an increased risk of nonbenign neoplasms, based on observed numerical imbalance versus placebo.\"},{\"question\":\"What mechanisms are proposed to explain the possible neoplastic risk?\",\"answer\":\"The review discusses reduced kisspeptin secretion, which may affect antimetastasis functions, and possible compensatory activation of neurokinin 1 receptor (NK1R), implicated in tumor proliferation and metastasis.\"}]","Potential risk of neoplasms with fezolinetant - clinical evidence, mechanisms, and post-marketing implications | PDF",1790101977]