title: Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy.
abstract: Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy.
  
  
  
  We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg(-1) for a maximum of four doses.
  
  
  
  Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (>6 months) stable disease. Thirty-five percent of patients developed grade 3-5 immune-related toxicity associated with ipilimumab therapy. The most common high-grade immune-related toxicity was diarrhoea. Three patients (7%) developed grade 3-5 pneumonitis leading to death in one patient.
  
  
  
  Ipilimumab therapy can induce responses in patients who fail the anti-PD-1 therapy with response rates comparable to previous reports. There appears to be an increased frequency of high-grade immune-related adverse events including pneumonitis that warrants close surveillance.
authors.affiliation: Rockingham General Hospital, Cooloongup, Western Australia, Australia.|School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Bowyer
authors.affiliation: Olivia Newton- John Cancer Centre, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia.|Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Prithviraj
authors.affiliation: The Christie NHS Foundation Trust and University of Manchester, Manchester, UK.
authors.forename: P
authors.initials: P
authors.lastname: Lorigan
authors.affiliation: Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Larkin
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: McArthur
authors.affiliation: Princess Alexandra Hospital, Greenslopes Private Hospital, Brisbane, Queensland, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Atkinson
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia.|Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Millward
authors.affiliation: Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Khou
authors.affiliation: Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Diem
authors.affiliation: Melanoma Institute Australia, Sydney, New South Wales, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ramanujam
authors.affiliation: Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Kong
authors.affiliation: Melanoma Institute Australia, Sydney, New South Wales, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Liniker
authors.affiliation: Melanoma Institute Australia, Sydney, New South Wales, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Guminski
authors.affiliation: Box Hill Hospital, Box Hill, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Parente
authors.affiliation: Olivia Newton- John Cancer Centre, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia.|Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, Victoria, Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Andrews
authors.affiliation: Olivia Newton- John Cancer Centre, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Parakh
authors.affiliation: Olivia Newton- John Cancer Centre, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia.|Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Cebon
authors.affiliation: Melanoma Institute Australia, Sydney, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
authors.forename: G V
authors.initials: GV
authors.lastname: Long
authors.affiliation: Westmead Hospital, Sydney, New South Wales, Australia.|Melanoma Institute Australia, Sydney, New South Wales, Australia.|University of Sydney, Sydney, New South Wales, Australia.
authors.forename: M S
authors.initials: MS
authors.lastname: Carlino
authors.affiliation: Olivia Newton- John Cancer Centre, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia.|Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, Victoria, Australia.
authors.forename: O
authors.initials: O
authors.lastname: Klein
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab