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

被引：1051

作者：

Gandara, David R. ^{[1
]}

Paul, Sarah M. ^{[2
]}

Kowanetz, Marcin ^{[2
]}

Schleifman, Erica ^{[2
]}

Zou, Wei ^{[2
]}

Li, Yan ^{[2
]}

Rittmeyer, Achim ^{[3
]}

Fehrenbacher, Louis ^{[4
]}

Otto, Geoff ^{[5
]}

Malboeuf, Christine ^{[5
]}

Lieber, Daniel S. ^{[5
]}

Lipson, Doron ^{[5
]}

Silterra, Jacob ^{[5
]}

Amler, Lukas ^{[2
]}

Riehl, Todd ^{[2
]}

Cummings, Craig A. ^{[2
]}

Hegde, Priti S. ^{[2
]}

Sandler, Alan ^{[2
]}

Ballinger, Marcus ^{[2
]}

Fabrizio, David ^{[5
]}

Mok, Tony ^{[6
]}

Shames, David S. ^{[2
]}

机构：

[1] UC Davis Comprehens Canc Ctr, Sacramento, CA USA

[2] Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA

[3] Lungenfachklin Immenhausen, Immenhausen, Germany

[4] Kaiser Permanente Med Ctr, Vallejo, CA USA

[5] Fdn Med Inc, Cambridge, MA USA

[6] Chinese Univ Hong Kong, Dept Clin Oncol, State Key Lab Southern China, Hong Kong, Hong Kong, Peoples R China

来源：

NATURE MEDICINE | 2018年 / 24卷 / 09期

关键词：

LIQUID BIOPSIES; PD-1; BLOCKADE; OPEN-LABEL; DOCETAXEL; DNA; NIVOLUMAB; PEMBROLIZUMAB; MULTICENTER; LANDSCAPE; EVOLUTION;

D O I：

10.1038/s41591-018-0134-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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-PDL1) in second-line and higher NSCLC. Collectively, our data show that high bTMB is a clinically actionable biomarker for atezolizumab in NSCLC.

引用

页码：1441 / +

页数：10

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