title: Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification.
abstract: OBJECTIVE
  Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications.
  
  
  METHODS
  Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d.
  
  
  RESULTS
  Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P < .001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD.
  
  
  CONCLUSIONS
  Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China. guoj307@126.com
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Lu
authors.initials: L
authors.lastname: Si
authors.forename: Yan
authors.initials: Y
authors.lastname: Kong
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Haifu
authors.initials: H
authors.lastname: Li
authors.forename: Xinan
authors.initials: X
authors.lastname: Sheng
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Cui
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Chi
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Lili
authors.initials: L
authors.lastname: Mao
authors.forename: Xuede
authors.initials: X
authors.lastname: Lin
authors.forename: Nan
authors.initials: N
authors.lastname: Du
authors.forename: Xiaoshi
authors.initials: X
authors.lastname: Zhang
authors.forename: Junling
authors.initials: J
authors.lastname: Li
authors.forename: Baocheng
authors.initials: B
authors.lastname: Wang
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D002681:China; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D005784:Gene Amplification; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000235:genetics*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit