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Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy

BACKGROUND: 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...

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Autores principales: Bowyer, S, Prithviraj, P, 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, J, Long, G V, Carlino, M S, Klein, O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865968/
https://www.ncbi.nlm.nih.gov/pubmed/27124339
http://dx.doi.org/10.1038/bjc.2016.107
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author Bowyer, S
Prithviraj, P
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, J
Long, G V
Carlino, M S
Klein, O
author_facet Bowyer, S
Prithviraj, P
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, J
Long, G V
Carlino, M S
Klein, O
author_sort Bowyer, S
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-48659682017-05-10 Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy Bowyer, S Prithviraj, P 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, J Long, G V Carlino, M S Klein, O Br J Cancer Clinical Study BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Nature Publishing Group 2016-05-10 2016-04-28 /pmc/articles/PMC4865968/ /pubmed/27124339 http://dx.doi.org/10.1038/bjc.2016.107 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Clinical Study
Bowyer, S
Prithviraj, P
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, J
Long, G V
Carlino, M S
Klein, O
Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy
title Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy
title_full Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy
title_fullStr Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy
title_full_unstemmed Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy
title_short Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy
title_sort efficacy and toxicity of treatment with the anti-ctla-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-pd-1 therapy
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865968/
https://www.ncbi.nlm.nih.gov/pubmed/27124339
http://dx.doi.org/10.1038/bjc.2016.107
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