Response to Cabozantinib in Patients with RET Fusion-Positive Lung Adenocarcinomas

作者：Alexander Edward Dela Cruz Drilon, Lu Wang, Adnan Hasanovic, Yoshiyuki Suehara, Doron Lipson, Phil J. Stephens, Jeffrey S. Ross, Vincent A. Miller, Michelle S. Ginsberg, Maureen Frances Zakowski, Mark G. Kris, Marc Ladanyi, Naiyer A. Rizvi · 发表于：Cancer Discovery · 年份：2013 · DOI：10.1158/2159-8290.cd-13-0035 · 被引用次数：471 · 研究领域：Lung Cancer Treatments and Mutations、Cancer-related gene regulation、Cancer Genomics and Diagnostics

Abstract 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. Significance: Driver oncogene discovery in lung cancers has dramatically changed today's therapeutic landscape. This report of the activity of cabozantinib in RET fusion-positive disease provides early clinical validation of RET fusions as drivers in lung cancers and suggests that RET inhibition may represent a new treatment paradigm in this molecular cohort. Cancer Discov; 3(6); 630–5. ©2013 AACR. See related commentary by Gainor and Shaw, p. 604 This article is highli...