A Gene Mutation Signature Predicting Immunotherapy Benefits in Patients With NSCLC.
A Gene Mutation Signature Predicting Immunotherapy Benefits in Patients With NSCLC.
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一种基因突变特征可预测NSCLC患者的免疫治疗获益。
DOI：
10.1016/j.jtho.2020.11.021
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Li CY
中科院分区：
文献类型：
--
作者：
Pan D;Hu AY;Antonia SJ;Li CY
识别可以从免疫检查点阻断（ICB）治疗中获益的患者是改善临床结局的关键。最近，美国FDA批准肿瘤突变负荷高（TMB-H，或TMB≥10）作为派姆单抗治疗实体瘤的生物标志物。我们打算检验这样一个假设，即与TMB-H相比，选择基因中的突变可能是非小细胞肺癌（NSCLC）对ICB治疗反应的更好预测因子。我们通过使用最近发表的350例NSCLC患者队列的数据，编制了一份候选基因列表，这些基因可能预测ICB治疗的益处。然后，我们评估了候选基因中不同突变特征对ICB疗效的影响。并与TMB-H进行了比较。然后在ICB治疗的非小细胞肺癌患者的独立队列中检查不同突变特征的预测能力。复合突变特征，其中52个候选基因中的两个或更多个突变，占350名NSCLC患者中的145名，并与显著的ICB治疗获益相关。具体而言，NSCLC中52个基因中有两个或更多突变的患者的中位总生存期（OS）为36个月，而非8个月。此外，与没有复合突变特征但TMB-H（≥ 10）的患者相比，具有复合突变特征但TMB较低（<10）的患者获得了显著的OS获益。最后，在一个由156名ICB治疗的NSCLC患者组成的独立队列中，52个基因中有复合突变特征的患者与无突变的患者的中位无进展生存期分别为8.3个月和3.5个月。在预测NSCLC患者ICB治疗的临床获益方面，52个候选基因中至少有2个发生突变的基因签名优于TMB-H上级。
Identification of patients who can benefit from immune checkpoint blockade (ICB) therapy is key for improved clinical outcome. Recently, US FDA approved tumor mutational load high (TMB-H, or TMB≥10) as a biomarker for pembrolizumab treatment of solid tumors. We intend to test the hypothesis that mutations in select genes may be a better predictor of non-small cell lung cancer (NSCLC) response to ICB therapy than TMB-H. We compiled a list of candidate genes that may predict for benefits from ICB treatment by use of data from a recently published cohort of 350 NSCLC patients. We then evaluated the influences of different mutation signatures in the candidate genes on ICB efficacy. They were also compared with TMB-H. The predictive powers of different mutation signatures were then examined in an independent cohort of ICB-treated non-small cell lung cancer patients. A compound mutation signature, where two or more of the 52 candidate genes were mutated, accounted for 145 of 350 NSCLC patients and was associated with significant ICB treatment benefits. Specifically, the median duration of overall survival (OS) was 36 vs 8 months in NSCLC in those with two or more vs none of the 52 genes mutated. Moreover, those patients with the compound mutation signature but low TMB (<10) achieved significant OS benefits when compared with those without the signature but TMB-H (≥10). Finally, in an independent cohort of 156 ICB-treated NSCLC patients the median duration of progression free survival was 8.3 months vs 3.5 months in those with the compound mutation signature vs those with none mutated in the 52 genes. A genetic signature with mutations in at least 2 of 52 candidate genes was superior than TMB-H in predicting clinical benefits for ICB therapy in NSCLC patients.
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影响因子：
3.7
作者：
Ghosh R;Roy S;Franco S
通讯作者：
Franco S
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：
64.5
作者：
Hugo W;Zaretsky JM;Sun L;Song C;Moreno BH;Hu-Lieskovan S;Berent-Maoz B;Pang J;Chmielowski B;Cherry G;Seja E;Lomeli S;Kong X;Kelley MC;Sosman JA;Johnson DB;Ribas A;Lo RS
通讯作者：
Lo RS
DOI：
10.1016/s0140-6736(16)32517-x
发表时间：
2017-01-21
期刊：
Lancet (London, England)
影响因子：
--
作者：
Rittmeyer A;Barlesi F;Waterkamp D;Park K;Ciardiello F;von Pawel J;Gadgeel SM;Hida T;Kowalski DM;Dols MC;Cortinovis DL;Leach J;Polikoff J;Barrios C;Kabbinavar F;Frontera OA;De Marinis F;Turna H;Lee JS;Ballinger M;Kowanetz M;He P;Chen DS;Sandler A;Gandara DR;OAK Study Group
通讯作者：
OAK Study Group
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM