title: Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma.
abstract: BACKGROUND
  Ipilimumab is an approved immunotherapy that has shown an overall survival benefit in patients with cutaneous metastatic melanoma in two phase III trials. As results of registrational trials might not answer all questions regarding safety and efficacy of ipilimumab in patients with advanced melanoma seen in daily clinical practice, the Dermatologic Cooperative Oncology Group conducted a phase II study to assess the efficacy and safety of ipilimumab in patients with different subtypes of metastatic melanoma.
  
  
  METHODS
  We undertook a multicenter phase II study in melanoma patients irrespective of location of the primary melanoma. Here we present data on patients with pretreated metastatic cutaneous, mucosal and occult melanoma 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
  103 pretreated patients received at least one dose of ipilimumab, including 83 cutaneous, seven mucosal and 13 occult melanomas. 1-year OS rates for cutaneous, mucosal and occult melanoma were 38 %, 14 % and 27 %, respectively. Median OS was 6.8 months (95 % CI 5.3-9.9) for cutaneous, 9.6 months (95 % CI 1.6-11.1) for mucosal, and 9.9 months (lower 95 % CI 2.3, upper 95 % CI non-existent) for occult melanoma. Overall response rates for cutaneous, mucosal and occult melanoma were 16 %, 17 % and 11 %, respectively. Eleven patients had partial response (16 %) and ten patients experienced stable disease (14 %), none achieved a complete response. Treatment-related AEs were observed in 71 patients (69 %), including 20 grade 3-4 events (19 %). No new and unexpected safety findings were noted.
  
  
  CONCLUSIONS
  Ipilimumab is a treatment option for pretreated patients with advanced cutaneous melanoma seen in daily routine. Toxicity was manageable when treated as per protocol-specific guidelines.
  
  
  BACKGROUND
  Clinical Trials.gov NCT01355120.
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany. lisa.zimmer@uk-essen.de.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen, Germany. thomas.eigentler@med.uni-tuebingen.de.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Eigentler
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany. felix.kiecker@charite.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Kiecker
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, Germany. Jan.simon@medizin.uni-leipzig.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Simon
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany. jochen.utikal@umm.de.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany. jochen.utikal@umm.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
authors.affiliation: Department of Dermatology, Elbekliniken Stade Buxtehude, Buxtehude, Germany. peter.mohr@elbekliniken.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Mohr
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany. carola.berking@med.uni-muenchen.de.
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
authors.affiliation: Department of Dermatology, Dermatologikum Berlin, Berlin, Germany. Kaempgen@dermatologikum-berlin.de.
authors.forename: Eckhart
authors.initials: E
authors.lastname: Kämpgen
authors.affiliation: Department of Dermatology, Klinikum Ludwigshafen, Skin Cancer Center Rheinpfalz, Ludwigshafen, Germany. dippele@klilu.de.
authors.forename: Edgar
authors.initials: E
authors.lastname: Dippel
authors.affiliation: Department of Dermatology, Medical Centre Minden, Minden, Germany. rudolf.stadler@muehlenkreiskliniken.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stadler
authors.affiliation: University Department of Dermatology, Kiel, Germany. ahauschild@dermatology.uni-kiel.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.affiliation: Department of Dermatology Hornheide, Münster, Germany. michael.fluck@fachklinik-hornheide.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Fluck
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany. patrick.terheyden@uksh.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Terheyden
authors.affiliation: Department of Dermatology, Clinical Centre Kassel, Kassel, Germany. rompel@klinikum-kassel.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rompel
authors.affiliation: Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany. Carmen.Loquai@unimedizin-mainz.de.
authors.forename: Carmen
authors.initials: C
authors.lastname: Loquai
authors.affiliation: Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen, Germany. zeinab.jradi.assi@gmail.com.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Assi
authors.affiliation: Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen, Germany. claus.garbe@uni-tuebingen.de.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany. dirk.schadendorf@uk-essen.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000074324:Ipilimumab