Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab.

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 Med

journal_title

Nature medicine

authors

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,Shames

doi

10.1038/s41591-018-0134-3

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

1441-1448

issue

9

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-018-0134-3

journal_volume

24

pub_type

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