Response to cabozantinib in patients with RET fusion-positive lung adenocarcinomas Journal Article
| Authors: | Drilon, A.; Wang, L.; Hasanovic, A.; Suehara, Y.; Lipson, D.; Stephens, P.; Ross, J.; Miller, V.; Ginsberg, M.; Zakowski, M. F.; Kris, M. G.; Ladanyi, M.; Rizvi, N. |
| Article Title: | Response to cabozantinib in patients with RET fusion-positive lung adenocarcinomas |
| 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. © 2013 American Association for Cancer Research. |
| Journal Title: | Cancer Discovery |
| Volume: | 3 |
| Issue: | 6 |
| ISSN: | 2159-8274 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2013-06-01 |
| Start Page: | 630 |
| End Page: | 635 |
| Language: | English |
| DOI: | 10.1158/2159-8290.cd-13-0035 |
| PROVIDER: | scopus |
| PUBMED: | 23533264 |
| PMCID: | PMC4160032 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 1 July 2013" - "Source: Scopus" |
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