Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas
Alexander Drilon, Lu Wang, Adnan Hasanovic, Yoshiyuki Suehara, Doron Lipson, Phil Stephens, Jeffrey Ross, Vincent Miller, Michelle Ginsberg, Maureen F Zakowski, Mark G Kris, Marc Ladanyi, Naiyer Rizvi, Alexander Drilon, Lu Wang, Adnan Hasanovic, Yoshiyuki Suehara, Doron Lipson, Phil Stephens, Jeffrey Ross, Vincent Miller, Michelle Ginsberg, Maureen F Zakowski, Mark G Kris, Marc Ladanyi, Naiyer Rizvi
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.
Conflict of interest statement
Disclosure of Potential Conflicts of Interest
D. Lipson is employed as Director of Foundation Medicine and has ownership interest (including patents) in the same. P. Stephens has ownership interest (including patents) in Foundation Medicine. J. Ross is employed as Medical Director of Foundation Medicine, has received a commercial research grant from Foundation Medicine, and has ownership interest (including patents) in the same. V. Miller is employed as Senior Vice President, Clinical Development, at Foundation Medicine and has ownership interest (including patents) in the same. M.G. Kris is a consultant/advisory board member of Pfizer, Inc. No potential conflicts of interest were disclosed by the other authors.
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Source: PubMed