Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas.
Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas.
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DOI：
10.1158/2159-8290.cd-13-0035
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发表时间：
2013-06
期刊：
影响因子：
28.2
通讯作者：
Rizvi N
中科院分区：
文献类型：
--
作者：
Drilon A;Wang L;Hasanovic A;Suehara Y;Lipson D;Stephens P;Ross J;Miller V;Ginsberg M;Zakowski MF;Kris MG;Ladanyi M;Rizvi N
肺癌中RET融合的发现为肿瘤携带这些变化的患者揭示了一个新的治疗靶点。在非小细胞肺癌（NSCLC）的非小细胞人群中，RET融合存在于1%至2%的病例中。然而，这种发病率在患有缺乏其他已知驱动癌基因的肺腺癌的从不吸烟者中显著增加。尽管临床前数据为使用RET抑制剂治疗RET融合阳性肿瘤提供了实验支持，但缺乏关于反应的临床数据。我们报告了在针对RET融合阳性NSCLC患者的前瞻性II期试验（NCT 01639508）中用RET抑制剂卡博替尼治疗的前三名患者的初步数据。在2例患者中观察到确认的部分缓解，包括1例携带新型TRIM 33-RET融合的患者。第三名KIF 5 B-RET融合患者的疾病长期稳定，接近8个月（31周）。所有三名患者在治疗中保持无进展。
The discovery of RET fusions in lung cancers has uncovered a new therapeutic target for patients whose tumors harbor these changes. In an unselected population of non–small cell lung carcinomas (NSCLCs), RET fusions are present in 1% to 2% of cases. This incidence increases substantially, however, in never-smokers with lung adenocarcinomas that lack other known driver oncogenes. Although preclinical data provide experimental support for the use of RET inhibitors in the treatment of RET fusion-positive tumors, clinical data on response are lacking. We report preliminary data for the first three patients treated with the RET inhibitor cabozantinib on a prospective phase II trial for patients with RET fusion-positive NSCLCs (NCT01639508). Confirmed partial responses were observed in 2 patients, including one harboring a novel TRIM33–RET fusion. A third patient with a KIF5B–RET fusion has had prolonged stable disease approaching 8 months (31 weeks). All three patients remain progression-free on treatment.