Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.
Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.
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DOI：
10.1016/j.ccell.2018.03.018
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发表时间：
2018-05-14
期刊：
影响因子：
50.3
通讯作者：
Wolchok JD
中科院分区：
文献类型：
--
作者：
Hellmann MD;Nathanson T;Rizvi H;Creelan BC;Sanchez-Vega F;Ahuja A;Ni A;Novik JB;Mangarin LMB;Abu-Akeel M;Liu C;Sauter JL;Rekhtman N;Chang E;Callahan MK;Chaft JE;Voss MH;Tenet M;Li XM;Covello K;Renninger A;Vitazka P;Geese WJ;Borghaei H;Rudin CM;Antonia SJ;Swanton C;Hammerbacher J;Merghoub T;McGranahan N;Snyder A;Wolchok JD
联合免疫检查点阻断已在肺癌中显示出有希望的益处，但对联合治疗的反应的预测因素尚不清楚。使用全外显子组测序检查PD-1加CTLA-4阻断治疗的非小细胞肺癌（NSCLC），我们发现高肿瘤突变负荷（TMB）预测改善的客观缓解，持久的益处和无进展生存期。TMB与PD-L1表达无关，是多变量分析中与疗效相关的最强特征。低TMB NSCLC中的低应答率表明，联合免疫疗法不能克服低TMB的阴性预测影响。本研究证明了TMB与NSCLC联合免疫治疗获益之间的相关性。TMB应纳入未来的试验，检查PD-（L）1与CTLA-4阻滞剂在NSCLC中的作用。高TMB与PD-1加CTLA-4阻断在NSCLC中的疗效相关TMB和PD-L1是独立变量在多变量分析中，TMB与疗效Hellmann et al.使用全外显子组测序检查联合PD-1和CTLA-4阻断治疗的非小细胞肺癌，发现高肿瘤突变负荷是多变量分析中与改善客观缓解、持久获益和无进展生存期相关的最强特征。
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis. The low response rate in TMB low NSCLCs demonstrates that combination immunotherapy does not overcome the negative predictive impact of low TMB. This study demonstrates the association between TMB and benefit to combination immunotherapy in NSCLC. TMB should be incorporated in future trials examining PD-(L)1 with CTLA-4 blockade in NSCLC. High TMB correlates with efficacy of PD-1 plus CTLA-4 blockade in NSCLC TMB and PD-L1 are independent variables In multivariate analysis, TMB associated most strongly with efficacy Hellmann et al. examine non-small-cell lung cancers treated with combined PD-1 and CTLA-4 blockade using whole-exome sequencing and find that high tumor mutation burden is the strongest feature associated with improved objective response, durable benefit, and progression-free survival in multivariable analysis.
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影响因子：
50.3
作者：
Hellmann MD;Callahan MK;Awad MM;Calvo E;Ascierto PA;Atmaca A;Rizvi NA;Hirsch FR;Selvaggi G;Szustakowski JD;Sasson A;Golhar R;Vitazka P;Chang H;Geese WJ;Antonia SJ
通讯作者：
Antonia SJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators
影响因子：
64.8
作者：
Burr ML;Sparbier CE;Chan YC;Williamson JC;Woods K;Beavis PA;Lam EYN;Henderson MA;Bell CC;Stolzenburg S;Gilan O;Bloor S;Noori T;Morgens DW;Bassik MC;Neeson PJ;Behren A;Darcy PK;Dawson SJ;Voskoboinik I;Trapani JA;Cebon J;Lehner PJ;Dawson MA
通讯作者：
Dawson MA