High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types

Annals of Oncology, Journal Year: 2021, Volume and Issue: 32(5), P. 661 - 672

Published: March 18, 2021

•TMB-H failed to predict improved or clinically relevant response ICB in all cancer types.•Cancer types where TMB-H does not generally show no relationship between tumor neoantigen load and CD8 T-cell infiltration.•Further studies should be carried out before application of as a biomarker for types. BackgroundHigh mutation burden (TMB-H) has been proposed predictive immune checkpoint blockade (ICB), largely due the potential mutations generate immunogenic neoantigens. Despite recent pan-cancer approval treatment any tumor, assessed by targeted FoundationOne CDx assay nine types, utility this fully demonstrated across cancers.Patients methodsData from over 10 000 patient tumors included The Cancer Genome Atlas were used compare approaches determine TMB identify correlation predicted T cells. Association with outcomes was analyzed both objective rates (ORRs, N = 1551) overall survival (OS, 1936).ResultsIn levels positively correlated load, such melanoma, lung, bladder cancers, exhibited 39.8% ORR [95% confidence interval (CI) 34.9-44.8], which significantly higher than that observed low (TMB-L) [odds ratio (OR) 4.1, 95% CI 2.9-5.8, P < 2 × 10−16]. In showed breast cancer, prostate glioma, achieve 20% (ORR 15.3%, 9.2-23.4, 0.95), lower relative TMB-L (OR 0.46, 0.24-0.88, 0.02). Bulk ORRs different two categories (P 0.10) cohorts assessed. Equivalent results obtained analyzing OS treating continuous variable.ConclusionsOur analysis support solid Further type-specific are warranted. High cancers. Data 1936). variable. Our

Language: Английский

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The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers

Cancer Cell, Journal Year: 2018, Volume and Issue: 34(3), P. 427 - 438.e6

Published: Sept. 1, 2018

Language: Английский

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Targeting mutant p53 for efficient cancer therapy

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 18(2), P. 89 - 102

Published: Dec. 15, 2017

Language: Английский

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Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(9), P. 495 - 509

Published: Aug. 12, 2019

Language: Английский

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The long tail of oncogenic drivers in prostate cancer

Nature Genetics, Journal Year: 2018, Volume and Issue: 50(5), P. 645 - 651

Published: March 23, 2018

Language: Английский

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