[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-458076-en":59,"doc-seo-458076-105":81},{"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":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":72,"language":73,"language_code":74,"site_id":75,"html_lang":74,"table_of_contents":76,"faqs":77,"seo_title":78,"seo_description":66,"update_tm":79,"read_time":80,"preview_page_count":4},458076,8796095461610,"Oliver","https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Immunotherapy for pleural mesothelioma: from innovation to the frontlines of core clinical questions","Immune checkpoint inhibitors have rapidly reshaped systemic therapy for pleural mesothelioma, beginning with Japan’s 2018 approval of nivolumab monotherapy and expanding through FDA approvals of nivolumab plus ipilimumab (CheckMate 743) and pembrolizumab plus platinum plus pemetrexed (KEYNOTE-483). The review synthesizes the latest evidence and expert insights to address urgent real-world clinical questions, including regimen choice, histologic subtype optimization, and post-progression options. It also examines biomarker utility such as PD-L1 expression.","Yoshida and Kuribayashi Discover Oncology (2026) 17:43  \n[https://doi.org/10.1007/s12672-025-04200-9](https://doi.org/10.1007/s12672-025-04200-9)  \nDiscover Oncology  \nREVIEW Open Access  \nImmunotherapy for pleural mesothelioma:  \nfrom innovation to the frontlines of core clinical questions  \nTatsuya Yoshida1† and Kozo Kuribayashi2*†  \n†Tatsuya Yoshida and Kozo Kuribayashi contributed equally.  \n*Correspondence:  \nKozo Kuribayashi[kuririn@hyo-med.ac.jp](kuririn@hyo-med.ac.jp)[ ](kuririn@hyo-med.ac.jp)1Department of Thoracic Oncology/ Experimental Therapeutics, National Cancer Centre Hospital, Tokyo, Japan  \n2Department of Respiratory Medicine and Hematology, Hyogo Medical University, 1-1, Mukogawacho, Nishinomiya 663-8501, Hyogo, Japan  \nAbstract  \nIn August 2018, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) became the first in the world to approve immune checkpoint inhibitor (ICI) monotherapy with nivolumab for previously treated, unresectable, advanced, or recurrent pleural mesothelioma (PM), setting a global precedent. Subsequently, in October 2020, the U. S. Food and Drug Administration (FDA) approved the combination of nivolumab and ipilimumab (CheckMate 743 trial) as the first-line treatment for unresectable PM. This marked the first update to standard first-line therapy in approximately 15 years since the approval of cisplatin (CDDP) plus pemetrexed (PEM) based on the EMPHACIS trial in 2004. Most recently, in September 2024, the FDA approved pembrolizumab plus platinum and PEM (KEYNOTE-483 trial) as another first-line option for advanced or metastatic PM. These developments underscore the rapid evolution of systemic therapy for PM. However, several urgent clinical questions have emerged in real-world practice. This article aims to address these issues based on the latest evidence and expert insights.  \n1 Introduction  \nSeveral systemic regimens for PM have now been approved by regulatory authorities worldwide:  \n• Cisplatin plus pemetrexed for untreated, unresectable PM (EMPHACIS trial) [1] .  \n• Nivolumab plus ipilimumab for untreated, unresectable PM (CheckMate 743 trial)[2] .  \n• Pembrolizumab plus platinum plus pemetrexed for untreated, unresectable PM (KEYNOTE-483 trial) [3] .  \n• Nivolumab monotherapy for previously treated PM (MERIT trial) [4] .  \nThe advent of ICIs has revolutionized the therapeutic landscape of PM [5]. Nevertheless, several unresolved clinical questions (CQs) have arisen in real-world practice:  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.)  \nYoshida and Kuribayashi Discover Oncology (2026) 17:43 Page 2 of 13  \nCQ1: Optimal selection between CheckMate 743 and KEYNOTE-483 regimens.  \nCQ2: Optimizing treatment strategies by histologic subtype (epithelioid vs.  \nnon-epithelioid).  \nSupplement: Insights from real-world evidence (RWE) following  \nnivolumab + ipilimumab.  \nCQ3: Treatment options after progression on CheckMate 743.  \nCQ4: Treatment options after progression on KEYNOTE-483.  \nSupplement: Do racial or ethnic differences influence outcomes of combination  \nimmunotherap","cbCain5gqfdojf6v","https://ap.wps.com/l/cbCain5gqfdojf6v","pdf",1504591,13,"English","en",105,"# Abstract\n# 1 Introduction\n## Approved systemic regimens and the emergence of ICIs\n## Core clinical questions (CQ1–CQ5) and supplements\n# 1.1 CQ1\n## Background\n## Efficacy in ITT populations\n## Safety (reporting framework for ITT)","[{\"question\":\"What major regulatory milestones accelerated immunotherapy for pleural mesothelioma?\",\"answer\":\"Japan approved nivolumab monotherapy in 2018, and the FDA later approved nivolumab plus ipilimumab (CheckMate 743) as first-line in 2020. In 2024, the FDA approved pembrolizumab plus platinum and pemetrexed (KEYNOTE-483) as another first-line option.\"},{\"question\":\"Which core clinical questions does the review focus on?\",\"answer\":\"The review highlights questions on optimal regimen selection between CheckMate 743 and KEYNOTE-483, treatment strategy optimization by histologic subtype, and management options after progression on each regimen. It also addresses whether racial/ethnic differences affect outcomes and whether PD-L1 is a reliable biomarker.\"},{\"question\":\"How should efficacy and safety outcomes from trials be interpreted and reported?\",\"answer\":\"The review states that cross-trial comparisons are inappropriate and each regimen should be interpreted within its own study context. It emphasizes consistent reporting of efficacy with HR, 95% CI, and p-values, along with specified assessment methods, and consistent safety summaries by grade and type across regimens.\"}]","Immunotherapy for pleural mesothelioma: from innovation to the frontlines of core clinical questions | PDF",1790751540,33,{"code":4,"msg":82,"data":83},"ok",{"site_id":75,"language":74,"slug":84,"title":65,"keywords":85,"description":66,"schema_data":86,"social_meta":140,"head_meta":142,"extra_data":144,"updated_unix":145},"immunotherapy-for-pleural-mesothelioma-from-innovation-to-the-frontlines-of-core-clinical-questions","",{"@graph":87,"@context":139},[88,102,122],{"@type":89,"itemListElement":90},"BreadcrumbList",[91,95,97,100],{"item":92,"name":93,"@type":94,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":96,"name":9,"@type":94,"position":14},"https://docshare.wps.com/document/",{"item":98,"name":35,"@type":94,"position":99},"https://docshare.wps.com/document/healthcare/",3,{"item":101,"name":65,"@type":94,"position":19},"https://docshare.wps.com/document/immunotherapy-for-pleural-mesothelioma-from-innovation-to-the-frontlines-of-core-clinical-questions/458076/",{"url":101,"name":65,"@type":103,"image":104,"author":109,"headline":65,"publisher":111,"fileFormat":114,"inLanguage":74,"description":66,"dateModified":115,"datePublished":116,"encodingFormat":114,"isAccessibleForFree":117,"interactionStatistic":118},"DigitalDocument",{"url":105,"@type":106,"width":107,"height":108},"https://docshare.wps.com/thumbnails/immunotherapy-for-pleural-mesothelioma-from-innovation-to-the-frontlines-of-core-clinical-questions/458076.png","ImageObject",300,407,{"name":63,"@type":110},"Person",{"url":92,"name":112,"@type":113},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":119,"interactionType":120,"userInteractionCount":52},"InteractionCounter",{"@type":121},"ViewAction",{"@type":123,"mainEntity":124},"FAQPage",[125,131,135],{"name":126,"@type":127,"acceptedAnswer":128},"What major regulatory milestones accelerated immunotherapy for pleural mesothelioma?","Question",{"text":129,"@type":130},"Japan approved nivolumab monotherapy in 2018, and the FDA later approved nivolumab plus ipilimumab (CheckMate 743) as first-line in 2020. In 2024, the FDA approved pembrolizumab plus platinum and pemetrexed (KEYNOTE-483) as another first-line option.","Answer",{"name":132,"@type":127,"acceptedAnswer":133},"Which core clinical questions does the review focus on?",{"text":134,"@type":130},"The review highlights questions on optimal regimen selection between CheckMate 743 and KEYNOTE-483, treatment strategy optimization by histologic subtype, and management options after progression on each regimen. It also addresses whether racial/ethnic differences affect outcomes and whether PD-L1 is a reliable biomarker.",{"name":136,"@type":127,"acceptedAnswer":137},"How should efficacy and safety outcomes from trials be interpreted and reported?",{"text":138,"@type":130},"The review states that cross-trial comparisons are inappropriate and each regimen should be interpreted within its own study context. It emphasizes consistent reporting of efficacy with HR, 95% CI, and p-values, along with specified assessment methods, and consistent safety summaries by grade and type across regimens.","https://schema.org",{"og:url":101,"og:type":141,"og:title":65,"og:site_name":112,"og:description":66},"article",{"robots":143,"canonical":101},"index,follow",{"doc_id":61,"site_id":75},1790790207]