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Title: Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy.
Austin Authors: Bowyer, S;Prithviraj, Prashanth;Lorigan, P;Larkin, J;McArthur, G;Atkinson, V;Millward, M;Khou, M;Diem, S;Ramanujam, S;Kong, B;Liniker, E;Guminski, A;Parente, P;Andrews, M C;Parakh, S ;Cebon, Jonathan S ;Long, G V;Carlino, M S;Klein, O 
Affiliation: Royal Marsden Hospital NHS Foundation Trust, London, UK
The Christie NHS Foundation Trust and University of Manchester, Manchester, UK
Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Westmead Hospital, Sydney, New South Wales, Australia
Box Hill Hospital, Box Hill, Victoria, Australia
Princess Alexandra Hospital, Greenslopes Private Hospital, Brisbane, Queensland, Australia
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
University of Sydney, Sydney, New South Wales, Australia
Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
School of Medicine and Pharmacology, University of Western Australia, Australia, Nedlands, Western Australia, Australia
Rockingham General Hospital, Cooloongup, Western Australia, Australia
Melanoma Institute Australia, Sydney, New South Wales, Australia
Issue Date: 10-May-2016
Date: 2016-04-28
Publication information: British Journal of Cancer 2016; 114(10): 1084-1089
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.
DOI: 10.1038/bjc.2016.107
ORCID: 0000-0002-3898-950X
Journal: British Journal of Cancer
PubMed URL: 27124339
Type: Journal Article
Appears in Collections:Journal articles

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