Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration.
Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration.
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DOI：
10.1038/s41591-019-0716-8
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发表时间：
2020-01
期刊：
影响因子：
82.9
通讯作者：
Paik PK
中科院分区：
文献类型：
--
作者：
Drilon A;Clark JW;Weiss J;Ou SI;Camidge DR;Solomon BJ;Otterson GA;Villaruz LC;Riely GJ;Heist RS;Awad MM;Shapiro GI;Satouchi M;Hida T;Hayashi H;Murphy DA;Wang SC;Li S;Usari T;Wilner KD;Paik PK
MET外显子14改变是非小细胞肺癌（NSCLC）的致癌驱动因素。这些改变与MET活性增加和对MET抑制的临床前敏感性相关。克唑替尼是一种多激酶抑制剂，对MET具有强效活性。在克唑替尼开放标签I期研究（NCT 00585195）的扩展队列中，在69例携带MET外显子14变异的晚期NSCLC患者中评估了克唑替尼的抗肿瘤活性和安全性。在65例缓解可评价患者中，确认的客观缓解率为32%（95%置信区间[CI]，21-45）。观察到的客观缓解与表征这些癌症的分子异质性无关，并且不因MET外显子14改变剪接位点区域和突变类型、同时增加的MET拷贝数或ctDNA中检测到MET外显子14改变而变化。中位缓解持续时间为9.1个月（95% CI，6.4-12.7）。中位无进展生存期为7.3个月（95% CI，5.4-9.1）。MET外显子14改变定义了克唑替尼对MET抑制有效的NSCLC分子亚组。这些结果解决了MET外显子14改变的肺癌患者对靶向治疗的未满足需求，并增加了针对NSCLC致癌子集的基因组驱动疗法的扩展列表。
MET exon 14 alterations are oncogenic drivers of non-small cell lung cancers (NSCLCs). These alterations are associated with increased MET activity and preclinical sensitivity to MET inhibition. Crizotinib is a multikinase inhibitor with potent activity against MET. The antitumor activity and safety of crizotinib were assessed in 69 patients with advanced NSCLCs harboring MET exon 14 alterations in an expansion cohort of an open-label phase 1 study of crizotinib (NCT00585195). The confirmed objective response rate was 32% (95% confidence interval [CI], 21–45) among 65 response-evaluable patients. Objective responses were observed independent of the molecular heterogeneity that characterizes these cancers and did not vary by MET exon 14 alteration splice site region and mutation type, concurrent increased MET copy number, or the detection of a MET exon 14 alteration in ctDNA. The median duration of response was 9.1 months (95% CI, 6.4–12.7). The median progression-free survival was 7.3 months (95% CI, 5.4–9.1). MET exon 14 alteration defines a molecular subgroup of NSCLCs for which MET inhibition with crizotinib is active. These results address an unmet need for targeted therapy in patients with MET exon 14-altered lung cancers and adds to an expanding list of genomically-driven therapies for oncogenic subsets of NSCLC.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
DOI：
10.1016/j.jtho.2016.04.033
发表时间：
2016-08
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Noonan SA;Berry L;Lu X;Gao D;Barón AE;Chesnut P;Sheren J;Aisner DL;Merrick D;Doebele RC;Varella-Garcia M;Camidge DR
通讯作者：
Camidge DR
影响因子：
45.3
作者：
Liu, Xuewen;Jia, Yuxia;Borczuk, Alain C.
通讯作者：
Borczuk, Alain C.
影响因子：
20.4
作者：
Lee, Carrie;Usenko, Dimitry;Weiss, Jared
通讯作者：
Weiss, Jared
影响因子：
3.6
作者：
Jenkins RW;Oxnard GR;Elkin S;Sullivan EK;Carter JL;Barbie DA
通讯作者：
Barbie DA