[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-374170-105":59,"doc-detail-374170-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","phase-i-trial-of-the-combination-of-the-pan-erbb-inhibitor-neratinib-and-mtor-inhibitor-everolimus-in-advanced-cancer-patients-with-erbb-family-gene-alterations","Phase I trial of the combination of the pan-ErbB inhibitor neratinib and mTOR inhibitor everolimus in advanced cancer patients with ErbB family gene alterations","","Phase I dose-escalation study evaluated neratinib, a pan-ErbB inhibitor, combined with everolimus, an mTOR inhibitor, in advanced cancers harboring ErbB family alterations. The trial assessed safety, tolerability, dose-limiting toxicities, and maximum tolerated dose, with secondary endpoints including RECIST v1.1 objective response and pharmacokinetic analyses. Twenty-two patients were enrolled; common treatment-related grade 3 events included diarrhea, anemia, mucositis, and acute kidney injury. The MTD was neratinib 240 mg with everolimus 7.5 mg, with a 19% objective response rate.",{"@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/phase-i-trial-of-the-combination-of-the-pan-erbb-inhibitor-neratinib-and-mtor-inhibitor-everolimus-in-advanced-cancer-patients-with-erbb-family-gene-alterations/374170/",{"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/phase-i-trial-of-the-combination-of-the-pan-erbb-inhibitor-neratinib-and-mtor-inhibitor-everolimus-in-advanced-cancer-patients-with-erbb-family-gene-alterations/374170.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main purpose of combining neratinib and everolimus in this phase I trial?","Question",{"text":112,"@type":113},"To evaluate the safety and efficacy of the combination in advanced cancers with ErbB family gene alterations, including determining dose-limiting toxicities and the maximum tolerated dose.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were patients selected for the trial?",{"text":117,"@type":113},"Patients with advanced cancers carrying ErbB family alterations were enrolled, including ErbB mutations, amplifications, or ErbB2 overexpression by immunohistochemistry.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key efficacy and dosing outcomes reported?",{"text":121,"@type":113},"The maximum tolerated dose was neratinib 240 mg with everolimus 7.5 mg, and the objective response rate was 19% with partial responses in four patients.","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},374170,1790246311,{"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":44,"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":145},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","ORIGINAL ARTICLE  \nPhase I trial of the combination of the pan-ErbB inhibitor neratinib and mTOR inhibitor everolimus in advanced cancer patients with ErbB family gene alterations  \nS. A. Piha-Paul1􀀁, C. Tseng1, H. T. Tran2, A. Naing1, E. E. Dumbrava1, D. D. Karp1, J. Rodon1, 3, T. A. Yap1 , 3, 4, K. P. Raghav5, S. Damodaran6, X. Le2, P. T. Soliman7, J. Lim8 & F. Meric-Bernstam1, 3 , 9  \nDepartments of 1Investigational Cancer Therapeutics (A Phase I Clinical Trials Program); 2Thoracic, Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston; 3The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston; 4Therapeutics Discovery Division, University of Texas MD Anderson Cancer Center, Houston; Departments of 5Gastrointestinal Medical Oncology; 6Breast Medical Oncology; 7Gynecologic Oncology & Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston; 8Pharmacy Clinic Programs, Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston; 9Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA  \nAvailable online xxx  \nBackground: The ErbB family of receptor tyrosine kinases are key targets for antitumor therapy. Although neratinib, a pan-ErbB kinase inhibitor, is approved in ErbB2-positive breast cancer, drug resistance is common. Preclinical data suggest that combining neratinib with the mTOR inhibitor everolimus may overcome such resistance.  \nPatients and methods: Our trial evaluated this combination’s safety and efficacy in advanced cancers with ErbB alterations. We conducted a phase I dose-escalation trial of neratinib and everolimus. Primary objectives were to assess safety, tolerability, and dose-limiting toxicities (DLTs) and establish the maximum tolerated dose (MTD) . Secondary objectives included objective response by RECIST v1.1 and pharmacokinetic analyses.  \nResults: Twenty-two patients (median age 61, median of four prior therapies) with ErbB alterations (mutations 63 .6%, amplification 36 .3%, or ErbB2-overexpressed by immunohistochemistry 9 . 1%) were enrolled. Common tumor types included breast (31 .8%), colorectal (18 . 2%), cervical (9 . 1%), and endometrial (9 . 1%) cancers. Frequent grade (G) 3 treatment-related adverse events were diarrhea (18.2%), anemia (9.1%), mucositis (9.1%), and acute kidney injury (9 . 1%) . DLTs included G3 mucositis and diarrhea at dose level (DL) 5, and G3 increased creatinine at DL4 . The MTD was DL4: neratinib 240 mg with everolimus 7.5 mg. The objective response rate was 19% with partial response in four patients. Stable disease 􀀃16 weeks was seen in two patients (9 .5%), resulting in a clinical benefit rate of 28 .6% . Conclusion: Pharmacokinetic data indicated reduced neratinib clearance possibly due to CYP3A4 pathway saturation by everolimus. Combination therapy with neratinib and everolimus has a tolerable safety profile and clinical activity in ErbB-altered patients. ErbB family receptors and the PI3K pathway are commonly implicated in oncogenesis. This clinical study of neratinib and everolimus demonstrated favorable clinical activity and tolerability.  \nKey words: neratinib, everolimus, ErbB-2, ErbB-3, ErbB-4, EGFR  \nINTRODUCTION  \nThe epidermal growth factor receptor family, consisting of four members including epidermal growth factor receptor (EGFR; ErbB1), human epidermal growth factor receptor (HER)-2/ErbB2, HER-3/ErbB3, and HER-4/ErbB4, collaborate to transmit extracellular signals to regulate fundamental cellular processes such as cell growth, metabolism,  \n*Correspondence to: Prof. Sarina A. Piha-Paul, 1515 Holcombe Blvd, Unit 455, Houston, TX 77030, USA. þ1-713-563-1055  \nE-mail: [spihapau@mdanderson.org](spihapau@mdanderson.org) (S. A. Piha-Paul).  \n2059-7029/© 2025 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access art","cbCaiuTwUw5OHzTy","https://ap.wps.com/l/cbCaiuTwUw5OHzTy","pdf",1224055,13,"English","# Background\n# Patients and methods\n# Results\n# Conclusion\n# Introduction","[{\"question\":\"What was the main purpose of combining neratinib and everolimus in this phase I trial?\",\"answer\":\"To evaluate the safety and efficacy of the combination in advanced cancers with ErbB family gene alterations, including determining dose-limiting toxicities and the maximum tolerated dose.\"},{\"question\":\"How were patients selected for the trial?\",\"answer\":\"Patients with advanced cancers carrying ErbB family alterations were enrolled, including ErbB mutations, amplifications, or ErbB2 overexpression by immunohistochemistry.\"},{\"question\":\"What were the key efficacy and dosing outcomes reported?\",\"answer\":\"The maximum tolerated dose was neratinib 240 mg with everolimus 7.5 mg, and the objective response rate was 19% with partial responses in four patients.\"}]","Phase I trial of the combination of the pan-ErbB inhibitor neratinib and mTOR inhibitor everolimus in advanced cancer patients with ErbB family gene alterations | PDF",1790201245,33]