title: Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition.
abstract: OBJECTIVE
  Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases are unknown.
  
  
  METHODS
  We conducted a phase II study of nilotinib 400 mg twice a day in two cohorts of patients with melanomas harboring KIT mutations or amplification: (A) those refractory or intolerant to a prior KIT inhibitor; and (B) those with brain metastases. The primary endpoint was 4-month disease control rate. Secondary endpoints included response rate, time-to-progression (TTP), and overall survival (OS). A Simon two-stage and a single-stage design was planned to assess for the primary endpoint in cohorts A and B, respectively.
  
  
  RESULTS
  Twenty patients were enrolled and 19 treated (11 in cohort A; 8 in cohort B). Three patients on cohort A [27%; 95% confidence interval (CI), 8%-56%] and 1 on cohort B (12.5%; 90% CI, 0.6%-47%) achieved the primary endpoint. Two partial responses were observed in cohort A (18.2%; 90% CI, 3%-47%); none were observed in cohort B. The median TTP and OS was 3.3 (90% CI, 2.1-3.9 months) and 9.1 months (90% CI, 4.3-14.2 months), respectively, in all treated patients.
  
  
  CONCLUSIONS
  Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy. The efficacy of this agent in KIT-altered melanoma with brain metastasis is limited.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York. Weill Medical College of Cornell University, New York, New York.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Lawrence
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, Florida.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.affiliation: The University of Chicago, Chicago, Illinois.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
authors.affiliation: The University of Colorado Cancer Center, Aurora, Colorado.
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Mount Sinai Comprehensive Cancer Center, Miami Beach, Florida.
authors.forename: Jose
authors.initials: J
authors.lastname: Lutzky
authors.affiliation: Beverly Hills Cancer Center, Beverly Hills, California.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: O'Day
authors.affiliation: Angeles Clinic and Research Institute, Los Angeles, California.
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York. Weill Medical College of Cornell University, New York, New York.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York. Weill Medical College of Cornell University, New York, New York.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jerrold B
authors.initials: JB
authors.lastname: Teitcher
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Ramaiya
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.affiliation: Oregon Health and Science University, Portland, Oregon.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.affiliation: The University of California San Francisco, San Francisco, California.
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
authors.affiliation: Oregon Health and Science University, Portland, Oregon.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts. Stephen_hodi@dfci.harvard.edu.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D019009:Proto-Oncogene Proteins c-kit; C498826:nilotinib