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Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis
Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300)...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511104/ https://www.ncbi.nlm.nih.gov/pubmed/34642329 http://dx.doi.org/10.1038/s41467-021-25859-y |
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author | Brastianos, Priscilla K. Strickland, Matthew R. Lee, Eudocia Quant Wang, Nancy Cohen, Justine V. Chukwueke, Ugonma Forst, Deborah Anne Eichler, April Overmoyer, Beth Lin, Nancy U. Chen, Wendy Y. Bardia, Aditya Juric, Dejan Dagogo-Jack, Ibiayi White, Michael D. Dietrich, Jorg Nayyar, Naema Kim, Albert E. Alvarez-Breckenridge, Christopher Mahar, Maura Mora, Joana L. Nahed, Brian V. Jones, Pamela S. Shih, Helen A. Gerstner, Elizabeth R. Giobbie-Hurder, Anita Carter, Scott L. Oh, Kevin Cahill, Daniel P. Sullivan, Ryan J. |
author_facet | Brastianos, Priscilla K. Strickland, Matthew R. Lee, Eudocia Quant Wang, Nancy Cohen, Justine V. Chukwueke, Ugonma Forst, Deborah Anne Eichler, April Overmoyer, Beth Lin, Nancy U. Chen, Wendy Y. Bardia, Aditya Juric, Dejan Dagogo-Jack, Ibiayi White, Michael D. Dietrich, Jorg Nayyar, Naema Kim, Albert E. Alvarez-Breckenridge, Christopher Mahar, Maura Mora, Joana L. Nahed, Brian V. Jones, Pamela S. Shih, Helen A. Gerstner, Elizabeth R. Giobbie-Hurder, Anita Carter, Scott L. Oh, Kevin Cahill, Daniel P. Sullivan, Ryan J. |
author_sort | Brastianos, Priscilla K. |
collection | PubMed |
description | Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results. |
format | Online Article Text |
id | pubmed-8511104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85111042021-10-29 Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis Brastianos, Priscilla K. Strickland, Matthew R. Lee, Eudocia Quant Wang, Nancy Cohen, Justine V. Chukwueke, Ugonma Forst, Deborah Anne Eichler, April Overmoyer, Beth Lin, Nancy U. Chen, Wendy Y. Bardia, Aditya Juric, Dejan Dagogo-Jack, Ibiayi White, Michael D. Dietrich, Jorg Nayyar, Naema Kim, Albert E. Alvarez-Breckenridge, Christopher Mahar, Maura Mora, Joana L. Nahed, Brian V. Jones, Pamela S. Shih, Helen A. Gerstner, Elizabeth R. Giobbie-Hurder, Anita Carter, Scott L. Oh, Kevin Cahill, Daniel P. Sullivan, Ryan J. Nat Commun Article Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results. Nature Publishing Group UK 2021-10-12 /pmc/articles/PMC8511104/ /pubmed/34642329 http://dx.doi.org/10.1038/s41467-021-25859-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Brastianos, Priscilla K. Strickland, Matthew R. Lee, Eudocia Quant Wang, Nancy Cohen, Justine V. Chukwueke, Ugonma Forst, Deborah Anne Eichler, April Overmoyer, Beth Lin, Nancy U. Chen, Wendy Y. Bardia, Aditya Juric, Dejan Dagogo-Jack, Ibiayi White, Michael D. Dietrich, Jorg Nayyar, Naema Kim, Albert E. Alvarez-Breckenridge, Christopher Mahar, Maura Mora, Joana L. Nahed, Brian V. Jones, Pamela S. Shih, Helen A. Gerstner, Elizabeth R. Giobbie-Hurder, Anita Carter, Scott L. Oh, Kevin Cahill, Daniel P. Sullivan, Ryan J. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis |
title | Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis |
title_full | Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis |
title_fullStr | Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis |
title_full_unstemmed | Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis |
title_short | Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis |
title_sort | phase ii study of ipilimumab and nivolumab in leptomeningeal carcinomatosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511104/ https://www.ncbi.nlm.nih.gov/pubmed/34642329 http://dx.doi.org/10.1038/s41467-021-25859-y |
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