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SCI 19 August 2018
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. 盡管PD-L1-PD-1抑制劑效用廣泛，具有高PD-L1表達(dá)或高腫瘤突變負(fù)荷（TMB）的患者的結(jié)局已有所改善,。在以免疫檢查點(diǎn)抑制劑單藥治療一線非小細(xì)胞肺癌（NSCLC）時(shí)需做PD-L1測(cè)試,。然而，在晚期患者中獲得足夠的腫瘤組織進(jìn)行分子測(cè)試卻十分困難,。因此,，不我們需要無(wú)需取組織就能識(shí)別哪些患者可能從免疫療法中獲益的診斷方法,，但這并未實(shí)現(xiàn)。 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. 在這里,，我們描述了一種新穎的,、技術(shù)上可靠的、基于血液的分析方法來(lái)測(cè)量血漿中的TMB(bTMB),，這與基于組織的方法是不同的,。通過(guò)將兩個(gè)大型隨機(jī)試驗(yàn)進(jìn)行的回顧性分析作為測(cè)試和驗(yàn)證研究，我們證明,，bTMB可重復(fù)識(shí)別出二線和更高的NSCLC人群中,，使用阿特佐朱單抗（抗PDL1）獲得臨床顯著改善的病人?？偟膩?lái)說(shuō),，我們的數(shù)據(jù)顯示，在NSCLC中,，高bTMB是一種臨床上可行的生物標(biāo)記物,。 作者；David R. Gandara1,7*, Sarah M. Paul2,7, Marcin Kowanetz2,7, Erica Schleifman2,7, Wei Zou2,7, Yan Li2, Achim Rittmeyer3, Louis Fehrenbacher4, Geoff Otto5, Christine Malboeuf5, Daniel S. Lieber5, Doron Lipson5, Jacob Silterra5, Lukas Amler2, Todd Riehl2, Craig A. Cummings2, Priti S. Hegde2, Alan Sandler2, Marcus Ballinger2, David Fabrizio5, Tony Mok6* and David S. Shames2* 作者單位：1UC Davis Comprehensive Cancer Center, Sacramento, CA, USA. 2Genentech, Inc., San Francisco, CA, USA. 3Lungenfachklinik Immenhausen, Immenhausen, Germany. 4Kaiser Permanente Medical Center, Vallejo, CA, USA. 5Foundation Medicine, Inc., Cambridge, MA, USA. 6State Key Laboratory of Southern China, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China. 7These authors contributed equally: David R. Gandara, Sarah M. Paul, Marcin Kowanetz, Erica Schleifman, Wei Zou. 出處：《NATURE MEDICINE》 喜歡SCI天天讀的理由 陪您一起學(xué)習(xí)SCI醫(yī)學(xué)論文 每天5分鐘,，讓自己的英語(yǔ)牛逼起來(lái) 特殊福利讓您驚喜連連 |
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