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A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma
Ipilimumab is an anti-CTLA4 monoclonal antibody with demonstrated efficacy for metastatic melanoma in randomized controlled trials, including in the first-line setting. Population-based outcomes directly compared with historic chemotherapy treatment in metastatic or unresectable melanoma are lacking...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887627/ https://www.ncbi.nlm.nih.gov/pubmed/30789386 http://dx.doi.org/10.1097/CMR.0000000000000582 |
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author | Drysdale, Erik Peng, Yingwei Nguyen, Paul Baetz, Tara Hanna, Timothy P. |
author_facet | Drysdale, Erik Peng, Yingwei Nguyen, Paul Baetz, Tara Hanna, Timothy P. |
author_sort | Drysdale, Erik |
collection | PubMed |
description | Ipilimumab is an anti-CTLA4 monoclonal antibody with demonstrated efficacy for metastatic melanoma in randomized controlled trials, including in the first-line setting. Population-based outcomes directly compared with historic chemotherapy treatment in metastatic or unresectable melanoma are lacking. Using population-based data from the province of Ontario, the benefit of first-line ipilimumab was estimated by comparing outcomes of patients treated with first-line dacarbazine over the period 2007–2009 with patients treated over the period 2010–2015 with first-line ipilimumab. Cutaneous and noncutaneous cases were included. The administrative data set utilized was high-dimensional; meaning, there was a large number of variables relative to the sample size. To adjust for important confounders among the many available variables, we utilized a double-selection method, a modified machine learning algorithm to extract the important variables that were related to both survival times and treatment usage. Time-dependent treatment modeling was utilized. Among the 2793 melanoma patients receiving palliative treatment (systemic therapy, surgery, or radiation) in Ontario (2007–2015), there were 289 patients treated with first-line ipilimumab (2010–2015) and 175 patients treated with first-line dacarbazine (2007–2009). For first-line ipilimumab, the adjusted hazard ratio compared with dacarbazine for overall survival (OS) was 0.63 (95% confidence interval: 0.47–0.84) with a 1-year survival of 46.5 versus 18.9% with dacarbazine. In subgroup analysis, ipilimumab was associated with improved OS across groups (age, sex, comorbidity, income quintile, previous interferon). First-line ipilimumab was found to have a significant OS benefit compared with historical controls in a population including those patients not routinely included in clinical trials. The treatment effect was similar to randomized controlled trials, suggesting a meaningful benefit when utilized in a population-based setting. |
format | Online Article Text |
id | pubmed-6887627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-68876272020-01-22 A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma Drysdale, Erik Peng, Yingwei Nguyen, Paul Baetz, Tara Hanna, Timothy P. Melanoma Res Original Articles: Clinical Research Ipilimumab is an anti-CTLA4 monoclonal antibody with demonstrated efficacy for metastatic melanoma in randomized controlled trials, including in the first-line setting. Population-based outcomes directly compared with historic chemotherapy treatment in metastatic or unresectable melanoma are lacking. Using population-based data from the province of Ontario, the benefit of first-line ipilimumab was estimated by comparing outcomes of patients treated with first-line dacarbazine over the period 2007–2009 with patients treated over the period 2010–2015 with first-line ipilimumab. Cutaneous and noncutaneous cases were included. The administrative data set utilized was high-dimensional; meaning, there was a large number of variables relative to the sample size. To adjust for important confounders among the many available variables, we utilized a double-selection method, a modified machine learning algorithm to extract the important variables that were related to both survival times and treatment usage. Time-dependent treatment modeling was utilized. Among the 2793 melanoma patients receiving palliative treatment (systemic therapy, surgery, or radiation) in Ontario (2007–2015), there were 289 patients treated with first-line ipilimumab (2010–2015) and 175 patients treated with first-line dacarbazine (2007–2009). For first-line ipilimumab, the adjusted hazard ratio compared with dacarbazine for overall survival (OS) was 0.63 (95% confidence interval: 0.47–0.84) with a 1-year survival of 46.5 versus 18.9% with dacarbazine. In subgroup analysis, ipilimumab was associated with improved OS across groups (age, sex, comorbidity, income quintile, previous interferon). First-line ipilimumab was found to have a significant OS benefit compared with historical controls in a population including those patients not routinely included in clinical trials. The treatment effect was similar to randomized controlled trials, suggesting a meaningful benefit when utilized in a population-based setting. Lippincott Williams & Wilkins 2019-12 2019-02-14 /pmc/articles/PMC6887627/ /pubmed/30789386 http://dx.doi.org/10.1097/CMR.0000000000000582 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NCND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Original Articles: Clinical Research Drysdale, Erik Peng, Yingwei Nguyen, Paul Baetz, Tara Hanna, Timothy P. A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma |
title | A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma |
title_full | A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma |
title_fullStr | A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma |
title_full_unstemmed | A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma |
title_short | A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma |
title_sort | population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma |
topic | Original Articles: Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887627/ https://www.ncbi.nlm.nih.gov/pubmed/30789386 http://dx.doi.org/10.1097/CMR.0000000000000582 |
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