title: Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06).
abstract: BACKGROUND
  KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications.
  
  
  METHODS
  We conducted a phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily. The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population.
  
  
  RESULTS
  Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5%), 15 (35.7%), and 2 (4.8%) patients had KIT mutations, KIT amplifications, and both KIT mutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7% (95% confidence interval [CI]: 5.4%-28.0%) and a disease control rate of 57.1% (95% CI: 42.1%-72.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KIT mutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only.
  
  
  CONCLUSIONS
  Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations.
  
  
  CONCLUSIONS
  KIT aberration can be detected in a subset of metastatic melanoma patients. This phase II trial showed that nilotinib demonstrates durable response in a subset of patients with KIT mutations. The safety profile was very tolerable. This study suggests that a KIT inhibitor may benefit a small subset of metastatic melanoma patients with KIT mutations.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pathology and Translational Genomics, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kee-Taek
authors.initials: KT
authors.lastname: Jang
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Hemato-Oncology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Soon Nam
authors.initials: SN
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Suee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Hemato-Oncology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea jyunlee@skku.edu.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000008:administration & dosage*
chemical_list: D011743:Pyrimidines; D019009:Proto-Oncogene Proteins c-kit; C498826:nilotinib
keywords: KIT amplification; KIT mutation; Melanoma; Nilotinib