title: Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma.
abstract: The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy.
  
  
  
  A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed.
  
  
  
  In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively.
  
  
  
  Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: lisa.zimmer@uk-essen.de.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Hematology/Oncology Fellowship Program, H Lee Moffitt Cancer Center and Research Institute/University of South Florida, Tampa, FL, USA.
authors.forename: Susmitha
authors.initials: S
authors.lastname: Apuri
authors.affiliation: Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Eroglu
authors.affiliation: Department of Oncology, Hematology and Immunology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kottschade
authors.affiliation: Department of Dermatology, University Hospital Tübingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Forschner
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Department of Dermatology, University Hospital Cologne, Skin Cancer Center, Center for Integrated Oncology (CIO) Köln Bonn, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Schlaak
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heinzerling
authors.affiliation: III. Medical Department, Technische Universität München (TUM) Munich, Germany.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Krackhardt
authors.affiliation: Department of Dermatology, University Hospital Mainz, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Loquai
authors.affiliation: Department of Oncology, Hematology and Immunology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.affiliation: Department of Oncology, Hematology and Immunology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Joseph
authors.affiliation: Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Markey
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 S
authors.initials: JS
authors.lastname: Utikal
authors.affiliation: Department of Dermatology, University Hospital Münster, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Weishaupt
authors.affiliation: Department of Dermatology, University Hospital Zurich, Switzerland.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Goldinger
authors.affiliation: Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.affiliation: Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Zager
authors.affiliation: Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Nikhil I
authors.initials: NI
authors.lastname: Khushalani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: Anti-PD-1; Disease progression; Efficacy; Ipilimumab; Ipilimumab and nivolumab; Melanoma; Nivolumab; Pembrolizumab; Treatment failure