Mutational Landscape of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Association with Immune Checkpoint Inhibitor Outcome

IF 10 1区 医学 Q1 ONCOLOGY
Patricia McCoon, Ying Wang, Zhongwu Lai, Qu Zhang, Weimin Li, Sophie Wildsmith, Nassim Morsli, Rajiv Raja, Nicholas Holoweckyj, Jill Walker, Melissa de los Reyes, Ricard Mesía, Lisa Licitra, Robert L. Ferris, Jérôme Fayette, Dan P. Zandberg, Lillian L. Siu, Robert Haddad
{"title":"Mutational Landscape of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Association with Immune Checkpoint Inhibitor Outcome","authors":"Patricia McCoon, Ying Wang, Zhongwu Lai, Qu Zhang, Weimin Li, Sophie Wildsmith, Nassim Morsli, Rajiv Raja, Nicholas Holoweckyj, Jill Walker, Melissa de los Reyes, Ricard Mesía, Lisa Licitra, Robert L. Ferris, Jérôme Fayette, Dan P. Zandberg, Lillian L. Siu, Robert Haddad","doi":"10.1158/1078-0432.ccr-24-2198","DOIUrl":null,"url":null,"abstract":"Purpose: Understanding the mutational landscape of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is important in identifying biomarkers to determine which patients may benefit from immune checkpoint inhibitors (ICIs). Patients and Methods: The HAWK (NCT02207530), CONDOR (NCT02319044), and EAGLE (NCT02369874) studies evaluated R/M HNSCC treatment with durvalumab or durvalumab-tremelimumab. Tumor tissue samples pooled from HAWK/CONDOR (n=153) and plasma cell-free DNA samples from EAGLE (n=285) were analyzed to identify somatic alterations and association with survival. Results: The mutational landscape was similar in tissue and plasma. Compared with wild-type, TP53 mutations were associated with significantly shorter OS (HR; 95% CI) with standard of care (SoC; 2.12; 1.20–3.78 EAGLE) and ICIs (1.49; 1.05–2.12; HAWK/CONDOR and 1.44; 0.99–2.10; EAGLE). In EAGLE, patients with TP53 mutations had significantly longer OS with durvalumab-tremelimumab versus SoC (P = 0.045). KMT2D mutations were associated with a trend towards longer OS (HR; 95% CI) versus wild-type in HAWK/CONDOR (0.81; 0.56–1.19), and a trend towards longer OS with ICIs versus SoC in EAGLE. For both mutations, an ECOG performance status of 1 was associated with worsened OS, and PD-L1 positivity was associated with improved OS. Conclusions: This is the first large-scale study to show the mutational landscape of R/M HNSCC and its association with clinical outcomes in patients treated with ICIs or SoC. TP53 mutation was a negative prognostic marker, however, treatment with durvalumab-tremelimumab significantly improved survival over SoC. Further investigation of KMT2D as a predictive biomarker for immunotherapy in R/M HNSCC is warranted.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"18 1","pages":""},"PeriodicalIF":10.0000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.ccr-24-2198","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: Understanding the mutational landscape of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is important in identifying biomarkers to determine which patients may benefit from immune checkpoint inhibitors (ICIs). Patients and Methods: The HAWK (NCT02207530), CONDOR (NCT02319044), and EAGLE (NCT02369874) studies evaluated R/M HNSCC treatment with durvalumab or durvalumab-tremelimumab. Tumor tissue samples pooled from HAWK/CONDOR (n=153) and plasma cell-free DNA samples from EAGLE (n=285) were analyzed to identify somatic alterations and association with survival. Results: The mutational landscape was similar in tissue and plasma. Compared with wild-type, TP53 mutations were associated with significantly shorter OS (HR; 95% CI) with standard of care (SoC; 2.12; 1.20–3.78 EAGLE) and ICIs (1.49; 1.05–2.12; HAWK/CONDOR and 1.44; 0.99–2.10; EAGLE). In EAGLE, patients with TP53 mutations had significantly longer OS with durvalumab-tremelimumab versus SoC (P = 0.045). KMT2D mutations were associated with a trend towards longer OS (HR; 95% CI) versus wild-type in HAWK/CONDOR (0.81; 0.56–1.19), and a trend towards longer OS with ICIs versus SoC in EAGLE. For both mutations, an ECOG performance status of 1 was associated with worsened OS, and PD-L1 positivity was associated with improved OS. Conclusions: This is the first large-scale study to show the mutational landscape of R/M HNSCC and its association with clinical outcomes in patients treated with ICIs or SoC. TP53 mutation was a negative prognostic marker, however, treatment with durvalumab-tremelimumab significantly improved survival over SoC. Further investigation of KMT2D as a predictive biomarker for immunotherapy in R/M HNSCC is warranted.
求助全文
约1分钟内获得全文 求助全文
来源期刊
Clinical Cancer Research
Clinical Cancer Research 医学-肿瘤学
CiteScore
20.10
自引率
1.70%
发文量
1207
审稿时长
2.1 months
期刊介绍: Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信