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.
authors.affiliation: Departments of Medicine Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drilon
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Adnan
authors.initials: A
authors.lastname: Hasanovic
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suehara
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.forename: Phil
authors.initials: P
authors.lastname: Stephens
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ross
authors.forename: Vincent
authors.initials: V
authors.lastname: Miller
authors.forename: Michelle
authors.initials: M
authors.lastname: Ginsberg
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Naiyer
authors.initials: N
authors.lastname: Rizvi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D050939:Gene Fusion; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011446:Prospective Studies; D051096:Proto-Oncogene Proteins c-ret / Q000096:biosynthesis* / Q000235:genetics; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000813:Anilides; D011725:Pyridines; C558660:cabozantinib; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human