Abstract:
:Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung cancer (NSCLC). However, obtaining adequate tumor tissue for molecular testing in patients with advanced disease can be challenging. Thus, an unmet medical need exists for diagnostic approaches that do not require tissue to identify patients who may benefit from immunotherapy. Here, we describe a novel, technically robust, blood-based assay to measure TMB in plasma (bTMB) that is distinct from tissue-based approaches. Using a retrospective analysis of two large randomized trials as test and validation studies, we show that bTMB reproducibly identifies patients who derive clinically significant improvements in progression-free survival from atezolizumab (an anti-PD-L1) in second-line and higher NSCLC. Collectively, our data show that high bTMB is a clinically actionable biomarker for atezolizumab in NSCLC.
journal_name
Nat Medjournal_title
Nature medicineauthors
Gandara DR,Paul SM,Kowanetz M,Schleifman E,Zou W,Li Y,Rittmeyer A,Fehrenbacher L,Otto G,Malboeuf C,Lieber DS,Lipson D,Silterra J,Amler L,Riehl T,Cummings CA,Hegde PS,Sandler A,Ballinger M,Fabrizio D,Mok T,Shamesdoi
10.1038/s41591-018-0134-3subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1441-1448issue
9eissn
1078-8956issn
1546-170Xpii
10.1038/s41591-018-0134-3journal_volume
24pub_type
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