Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab
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AbstractAlthough 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.
All Author(s) ListDavid R. Gandara, Sarah M. Paul, Marcin Kowanetz, Erica Schleifman, Wei Zou, Yan Li, Achim Rittmeyer, Louis Fehrenbacher, Geoff Otto, Christine Malboeuf, Daniel S. Lieber, Doron Lipson, Jacob Silterra, Lukas Amler, Todd Riehl, Craig A. Cummings, Priti S. Hegde, Alan Sandler, Marcus Ballinger, David Fabrizio, Tony Mok, David S. Shames
Journal nameNature Medicine
Year2018
Month9
Volume Number24
Pages1441 - 1448
ISSN1078-8956
eISSN1546-170X
LanguagesEnglish-United Kingdom
KeywordsNSCLC

Last updated on 2020-27-06 at 02:03