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Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma

Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in patients with metastatic UM, we analyzed the real-world outcomes in a nationwide popula...

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Autores principales: Bol, Kalijn Fredrike, Ellebaek, Eva, Hoejberg, Lise, Bagger, Mette Marie, Larsen, Mathilde Skaarup, Klausen, Tobias Wirenfeldt, Køhler, Ulrich Heide, Schmidt, Henrik, Bastholt, Lars, Kiilgaard, Jens Folke, Donia, Marco, Svane, Inge Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826482/
https://www.ncbi.nlm.nih.gov/pubmed/31623302
http://dx.doi.org/10.3390/cancers11101489
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author Bol, Kalijn Fredrike
Ellebaek, Eva
Hoejberg, Lise
Bagger, Mette Marie
Larsen, Mathilde Skaarup
Klausen, Tobias Wirenfeldt
Køhler, Ulrich Heide
Schmidt, Henrik
Bastholt, Lars
Kiilgaard, Jens Folke
Donia, Marco
Svane, Inge Marie
author_facet Bol, Kalijn Fredrike
Ellebaek, Eva
Hoejberg, Lise
Bagger, Mette Marie
Larsen, Mathilde Skaarup
Klausen, Tobias Wirenfeldt
Køhler, Ulrich Heide
Schmidt, Henrik
Bastholt, Lars
Kiilgaard, Jens Folke
Donia, Marco
Svane, Inge Marie
author_sort Bol, Kalijn Fredrike
collection PubMed
description Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in patients with metastatic UM, we analyzed the real-world outcomes in a nationwide population-based study. Clinical data of patients with UM were extracted from the Danish Metastatic Melanoma database, a nationwide database containing unselected records of patients diagnosed with metastatic melanoma in Denmark. Survival before (pre-ICI, n = 32) and after (post-ICI, n = 94) the approval of first-line treatment with ICI was analyzed. A partial response to first-line treatment was observed in 7% of patients treated with anti-programmed cell death protein (PD)-1 monotherapy and in 21% with combined anti-cytotoxic T lymphocyte antigen (CTLA)-4 plus anti-PD-1 therapy. Median progression-free survival was 2.5 months for patients treated in the pre-ICI era compared to 3.5 months in the post-ICI era (hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.28–0.67; p < 0.001). The estimated one-year overall survival rate increased from 25.0% to 41.9% and the median overall survival improved from 7.8 months to 10.0 months, respectively (HR 0.52; 95% CI 0.34–0.79; p = 0.003). Thus, the introduction of ICI as first-line treatment appears to have significantly improved the real-world survival of patients with metastatic UM, despite relatively low response rates compared to cutaneous melanoma. With the lack of therapies proven effective in randomized trials, these data support the current treatment with ICI in patients with metastatic UM.
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spelling pubmed-68264822019-11-18 Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma Bol, Kalijn Fredrike Ellebaek, Eva Hoejberg, Lise Bagger, Mette Marie Larsen, Mathilde Skaarup Klausen, Tobias Wirenfeldt Køhler, Ulrich Heide Schmidt, Henrik Bastholt, Lars Kiilgaard, Jens Folke Donia, Marco Svane, Inge Marie Cancers (Basel) Article Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in patients with metastatic UM, we analyzed the real-world outcomes in a nationwide population-based study. Clinical data of patients with UM were extracted from the Danish Metastatic Melanoma database, a nationwide database containing unselected records of patients diagnosed with metastatic melanoma in Denmark. Survival before (pre-ICI, n = 32) and after (post-ICI, n = 94) the approval of first-line treatment with ICI was analyzed. A partial response to first-line treatment was observed in 7% of patients treated with anti-programmed cell death protein (PD)-1 monotherapy and in 21% with combined anti-cytotoxic T lymphocyte antigen (CTLA)-4 plus anti-PD-1 therapy. Median progression-free survival was 2.5 months for patients treated in the pre-ICI era compared to 3.5 months in the post-ICI era (hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.28–0.67; p < 0.001). The estimated one-year overall survival rate increased from 25.0% to 41.9% and the median overall survival improved from 7.8 months to 10.0 months, respectively (HR 0.52; 95% CI 0.34–0.79; p = 0.003). Thus, the introduction of ICI as first-line treatment appears to have significantly improved the real-world survival of patients with metastatic UM, despite relatively low response rates compared to cutaneous melanoma. With the lack of therapies proven effective in randomized trials, these data support the current treatment with ICI in patients with metastatic UM. MDPI 2019-10-03 /pmc/articles/PMC6826482/ /pubmed/31623302 http://dx.doi.org/10.3390/cancers11101489 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bol, Kalijn Fredrike
Ellebaek, Eva
Hoejberg, Lise
Bagger, Mette Marie
Larsen, Mathilde Skaarup
Klausen, Tobias Wirenfeldt
Køhler, Ulrich Heide
Schmidt, Henrik
Bastholt, Lars
Kiilgaard, Jens Folke
Donia, Marco
Svane, Inge Marie
Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma
title Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma
title_full Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma
title_fullStr Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma
title_full_unstemmed Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma
title_short Real-World Impact of Immune Checkpoint Inhibitors in Metastatic Uveal Melanoma
title_sort real-world impact of immune checkpoint inhibitors in metastatic uveal melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826482/
https://www.ncbi.nlm.nih.gov/pubmed/31623302
http://dx.doi.org/10.3390/cancers11101489
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