| Literature DB >> 30643254 |
Robert M Samstein1,2, Chung-Han Lee3,4, Alexander N Shoushtari3,4, Matthew D Hellmann3,4, Ronglai Shen5, Yelena Y Janjigian3,4, David A Barron1,2, Ahmet Zehir6, Emmet J Jordan2, Antonio Omuro7, Thomas J Kaley7, Sviatoslav M Kendall2,8, Robert J Motzer3,4, A Ari Hakimi9, Martin H Voss3,4, Paul Russo9, Jonathan Rosenberg3,4, Gopa Iyer3,4, Bernard H Bochner9, Dean F Bajorin3,4, Hikmat A Al-Ahmadie6, Jamie E Chaft3,4, Charles M Rudin3,4, Gregory J Riely3,4, Shrujal Baxi3,4, Alan L Ho3,4, Richard J Wong9, David G Pfister3,4, Jedd D Wolchok3,4, Christopher A Barker1, Philip H Gutin9, Cameron W Brennan9, Viviane Tabar9, Ingo K Mellinghoff8, Lisa M DeAngelis8, Charlotte E Ariyan9, Nancy Lee1, William D Tap3,4, Mrinal M Gounder3,4, Sandra P D'Angelo3,4, Leonard Saltz3,4, Zsofia K Stadler3,4, Howard I Scher3,4, Jose Baselga3,4, Pedram Razavi3,4, Christopher A Klebanoff3,4, Rona Yaeger3,4, Neil H Segal3,4, Geoffrey Y Ku3,4, Ronald P DeMatteo9, Marc Ladanyi2,6, Naiyer A Rizvi10, Michael F Berger3,6, Nadeem Riaz1,2,8, David B Solit11,12, Timothy A Chan13,14,15, Luc G T Morris16,17,18.
Abstract
Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.Entities:
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Year: 2019 PMID： 30643254 PMCID： PMC6365097 DOI： 10.1038/s41588-018-0312-8
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330