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A retrospective observational study used de-identified electronic medical records from Flatiron Health Clinico-Genomic and FoundationCore databases to assess non-actionable mutation prevalence and their association with overall survival in routine first-line treatment from 2016 to 2021. Among 2999 patients and 185 mutations, STK11, KEAP1, and CDKN2A/B linked to poorer real-world response, progression-free survival, and overall survival.",{"@graph":69,"@context":123},[70,84,106],{"@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/identification-of-non-actionable-mutations-with-prognostic-and-predictive-value-in-patients-with-advanced-or-metastatic-non-small-cell-lung-cancer/341220/",{"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/identification-of-non-actionable-mutations-with-prognostic-and-predictive-value-in-patients-with-advanced-or-metastatic-non-small-cell-lung-cancer/341220.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What was the study’s primary objective?","Question",{"text":113,"@type":114},"To assess the prevalence of non-actionable mutations and determine their association with overall survival in real-world aNSCLC patients receiving first-line treatment.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was the real-world patient cohort constructed?",{"text":118,"@type":114},"The study analyzed de-identified electronic medical records from Flatiron Health Clinico-Genomic and FoundationCore databases for patients who initiated first-line immune checkpoint inhibitors or chemotherapy between 2016 and 2021.",{"name":120,"@type":111,"acceptedAnswer":121},"Which non-actionable mutations showed the strongest prognostic and predictive associations?",{"text":122,"@type":114},"STK11, KEAP1, and CDKN2A/B mutations were significantly associated with lower real-world response and shorter real-world progression-free survival and overall survival.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},341220,1790094382,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"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},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","Clinical and Translational Oncology (2024) 26:1384–1394  \n[https://doi.org/10.1007/s12094-023-03362-8](https://doi.org/10.1007/s12094-023-03362-8)  \nIdentification of non‑actionable mutations with prognostic and predictive value in patients with advanced or metastatic non‑small cell lung cancer  \nMariano Provencio‑Pulla1 · Diego Pérez‑Parente2 · Sara Olson2 · Haroon Hasan3 · Begoña Campos Balea4 · Delvys Rodríguez‑Abreu5 · Marta López‑Brea Piqueras6 · Navdeep Pal3 · Samantha Wilkinson7 ·  \nEsther Vilas2 · Pedro Ruiz‑Gracia2 · Manuel Cobo‑Dols8  \nReceived: 5 September 2023 / Accepted: 26 November 2023 / Published online: 6 January 2024 © The Author(s) 2023  \nAbstract  \nIntroduction Lung cancer is one of the most prevalent cancers and the leading cause of cancer death. Advanced non-small cell lung cancer (aNSCLC) patients frequently harbor mutations that impact their survival outcomes. There are limited data regarding the prognostic and predictive significance of these mutations on survival outcomes in the real-world setting. Methods This observational retrospective study analyzed de-identified electronic medical records from the Flatiron Health Clinico-Genomic and FoundationCore® databases to identify patients with aNSCLC who initiated first-line immune checkpoint inhibitors (ICI; alone or in combination) or chemotherapy under routine care between 2016 and 2021. The primary objectives were to assess the prevalence of non-actionable mutations and to determine their association with overall survival (OS). Real-world progression-free survival (rwPFS) and real-world response (rwR) were investigated as secondary exploratory outcomes.  \nResults Based on an assessment of 185 non-actionable mutations in 2999 patients, the most prevalent mutations were TP53 (70%), KRAS (42%), CDKN2A/B (31%), and STK11 (21%) . STK11, KEAP1, and CDKN2A/B mutations were significantly associated with lower rwR, shorter rwPFS and OS. KRAS mutations were clinically associated with shorter rwPFS in CITtreated patients. Subgroup analysis revealed that fast progressors were significantly more likely to harbor STK11, KEAP1, and CDKN2A/B mutations. Accordingly, long-term survivors (LTS) showed a significantly lower prevalence of these mutations. Conclusion Our results provide evidence on the prognostic value of STK11, KEAP1, and CDKN2A/B mutations in patients with aNSCLC. Further research is required to better understand the implications of these findings on patient management and future trial design and treatment selection.  \nKeywords NSCLC · Non-actionable mutations · Prognosis · Real-world · Survival  \n* Diego Pérez-Parente [diego.perez@roche.com](diego.perez@roche.com)  \n1 Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain  \n2 Lung Cancer Squad, Roche Farma SA, C. de La Ribera del Loira, 50, 28042 Madrid, Spain  \n3 Product Development Data Sciences, Genentech Inc, San Francisco, CA, USA  \n4 Hospital Universitario Lucus Augusti, Lugo, Spain  \n5 Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain  \n6 Hospital Marqués de Valdecilla, Santander, Spain  \n7 Product Development, Roche, Welwyn Garden City, UK  \n8 Hospital Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain  \nIntroduction  \nLung cancer is the second most diagnosed cancer worldwide and the leading cause of cancer death to date [1] . Based on histology, it can be classified into small cell lung cancer and non-small cell lung cancer (NSCLC), which approximately represent 25% and 85% of lung cancer diagnoses, respectively. NSCLC can be further classified into lung adenocarcinoma (45–60%), squamous cell carcinoma (20–25%), and neuroendocrine carcinoma (10–15%), which are treated using diverse therapeutic strategies. Recently, the development of new targeted therapies and the use of immunotherapy have increased 5-year overall survival (OS) rates in patients with NSCLC [2 , 3] . However, it remains unclea","cbCaifEMOuo4OzGv","https://ap.wps.com/l/cbCaifEMOuo4OzGv","pdf",1397839,"English","# Abstract\n# Introduction\n# Methods\n# Results\n# Conclusion","[{\"question\":\"What was the study’s primary objective?\",\"answer\":\"To assess the prevalence of non-actionable mutations and determine their association with overall survival in real-world aNSCLC patients receiving first-line treatment.\"},{\"question\":\"How was the real-world patient cohort constructed?\",\"answer\":\"The study analyzed de-identified electronic medical records from Flatiron Health Clinico-Genomic and FoundationCore databases for patients who initiated first-line immune checkpoint inhibitors or chemotherapy between 2016 and 2021.\"},{\"question\":\"Which non-actionable mutations showed the strongest prognostic and predictive associations?\",\"answer\":\"STK11, KEAP1, and CDKN2A/B mutations were significantly associated with lower real-world response and shorter real-world progression-free survival and overall survival.\"}]","Identification of non‑actionable mutations with prognostic and predictive value in patients with advanced or metastatic non‑small cell lung cancer | PDF",1790040996,28]