title: Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma.
abstract: OBJECTIVE
  Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.
  
  
  METHODS
  We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.
  
  
  RESULTS
  Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1), median progression-free survival 2.8 months (95% CI 2.5-2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3-4 events (36%). One drug-related death due to pancytopenia was observed.
  
  
  CONCLUSIONS
  Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01355120.
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Vaubel
authors.affiliation: Department of Dermatology, Buxtehude, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Mohr
authors.affiliation: University Department of Dermatology, Kiel, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
authors.affiliation: University Department of Dermatology, Leipzig, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Simon
authors.affiliation: University Department of Dermatology, Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Department of Dermatology, Erfurt, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Herbst
authors.affiliation: Department of Dermatology, University Hospital, Ruprecht-Karl University of Heidelberg, Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Enk
authors.affiliation: Department of Dermatology, University Hospital, Erlangen, Germany.
authors.forename: Eckhart
authors.initials: E
authors.lastname: Kämpgen
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Livingstone
authors.affiliation: Department of Dermatology, Buxtehude, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Bluhm
authors.affiliation: Department of Dermatology, Kassel, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rompel
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Griewank
authors.affiliation: Department of Dermatology Hornheide, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fluck
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schilling
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D049690:History, Ancient; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab