Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.
Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.
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DOI：
10.1001/jama.2014.3741
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发表时间：
2014-05-21
影响因子：
120.7
通讯作者：
Bunn, Paul A.
中科院分区：
文献类型：
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作者：
Kris, Mark G.;Johnson, Bruce E.;Berry, Lynne D.;Kwiatkowski, David J.;Iafrate, A. John;Wistuba, Ignacio I.;Varella-Garcia, Marileila;Franklin, Wilbur A.;Aronson, Samuel L.;Su, Pei-Fang;Shyr, Yu;Camidge, D. Ross;Sequist, Lecia V.;Glisson, Bonnie S.;Khuri, Fadlo R.;Garon, Edward B.;Pao, William;Rudin, Charles;Schiller, Joan;Haura, Eric B.;Socinski, Mark;Shirai, Keisuke;Chen, Heidi;Giaccone, Giuseppe;Ladanyi, Marc;Kugler, Kelly;Minna, John D.;Bunn, Paul A.
靶向致癌驱动因子（对癌症发展和维持至关重要的基因组改变）已经改变了肺腺癌患者的护理。肺癌突变联盟的成立是为了进行多重检测，检测肺腺癌的10个基因中的驱动因子，使临床医生能够选择靶向治疗并将患者纳入临床试验。确定肺腺癌患者中致癌驱动因子的频率，并使用这些数据选择靶向已识别驱动因子的治疗方法并测量生存率。从2009年到2012年，美国的14个研究中心招募了转移性肺腺癌患者，体能状态为0到2，并对他们的肿瘤进行了10项驱动因素的测试。收集患者、治疗和生存率的信息。对肿瘤进行了10种致癌驱动因素的测试，并将结果用于选择匹配的靶向治疗。确定致癌驱动基因的频率、接受基因型定向治疗的患者比例和生存率。从2009年到2012年，对1007名患者的肿瘤进行了至少1个基因的检测，对733名患者进行了10个基因的检测（患者具有完整的基因分型）。在733例患者中的466例（64%）中发现了致癌驱动因素。在这733例肿瘤中，182例肿瘤（25%）有KRAS驱动因子; 122例（17%）有致敏EGFR; 57例（8%）有ALK重排; 29例（4%）有其他EGFR; 24例（3%）有2种或2种以上基因; ERBB 2（以前称为HER 2），19例（3%）; BRAF，16例（2%）; PIK 3CA，6例（<1%）; MET扩增，5例（<1%）; NRAS，5例（<1%）; MEK 1，1例（<1%）; AKT 1，0例。结果用于选择1007例患者中的275例（28%）的靶向治疗或试验。中位生存期为3.5年（四分位距[IQR]，1.96-7.70），与2.4年相比，（IQR，0.88-6.20）对于318例未接受基因型定向治疗的具有任何致癌驱动因素的患者（倾向评分调整的风险比，0.69 [95% CI，0.53-0.9]，P = .006）。在64%的肺腺癌中检测到可操作的驱动因素。多重检测有助于医生选择治疗方法。尽管接受匹配靶向药物的驱动因素的个体寿命更长，但需要随机试验来确定基于致癌驱动因素的靶向治疗是否可以改善生存率。
Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score–adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
82.9
作者：
Kohno T;Ichikawa H;Totoki Y;Yasuda K;Hiramoto M;Nammo T;Sakamoto H;Tsuta K;Furuta K;Shimada Y;Iwakawa R;Ogiwara H;Oike T;Enari M;Schetter AJ;Okayama H;Haugen A;Skaug V;Chiku S;Yamanaka I;Arai Y;Watanabe S;Sekine I;Ogawa S;Harris CC;Tsuda H;Yoshida T;Yokota J;Shibata T
通讯作者：
Shibata T
有效使用 PI3K 和 MEK 抑制剂治疗突变型 Kras G12D 和 PIK3CA H1047R 小鼠肺癌。
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1158/1078-0432.ccr-12-0912
发表时间：
2012-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arcila ME;Chaft JE;Nafa K;Roy-Chowdhuri S;Lau C;Zaidinski M;Paik PK;Zakowski MF;Kris MG;Ladanyi M
通讯作者：
Ladanyi M
影响因子：
28.2
作者：
Hammerman PS;Sos ML;Ramos AH;Xu C;Dutt A;Zhou W;Brace LE;Woods BA;Lin W;Zhang J;Deng X;Lim SM;Heynck S;Peifer M;Simard JR;Lawrence MS;Onofrio RC;Salvesen HB;Seidel D;Zander T;Heuckmann JM;Soltermann A;Moch H;Koker M;Leenders F;Gabler F;Querings S;Ansén S;Brambilla E;Brambilla C;Lorimier P;Brustugun OT;Helland A;Petersen I;Clement JH;Groen H;Timens W;Sietsma H;Stoelben E;Wolf J;Beer DG;Tsao MS;Hanna M;Hatton C;Eck MJ;Janne PA;Johnson BE;Winckler W;Greulich H;Bass AJ;Cho J;Rauh D;Gray NS;Wong KK;Haura EB;Thomas RK;Meyerson M
通讯作者：
Meyerson M