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Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma
Despite markedly improved treatment options for metastatic melanoma, resistance to targeted therapies such as BRAF inhibitors (BRAFi) or BRAFi plus MEK inhibitors (MEKi) remains a major problem. Our aim was to characterize progression on BRAFi therapy and outcome of subsequent treatment. One hundred...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773979/ https://www.ncbi.nlm.nih.gov/pubmed/29266761 http://dx.doi.org/10.1002/cam4.1267 |
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author | Hassel, Jessica C. Buder‐Bakhaya, Kristina Bender, Carolin Zimmer, Lisa Weide, Benjamin Loquai, Carmen Ugurel, Selma Slynko, Alla Gutzmer, Ralf |
author_facet | Hassel, Jessica C. Buder‐Bakhaya, Kristina Bender, Carolin Zimmer, Lisa Weide, Benjamin Loquai, Carmen Ugurel, Selma Slynko, Alla Gutzmer, Ralf |
author_sort | Hassel, Jessica C. |
collection | PubMed |
description | Despite markedly improved treatment options for metastatic melanoma, resistance to targeted therapies such as BRAF inhibitors (BRAFi) or BRAFi plus MEK inhibitors (MEKi) remains a major problem. Our aim was to characterize progression on BRAFi therapy and outcome of subsequent treatment. One hundred and eighty patients with BRAF‐mutant metastatic melanoma who had progressed on treatment with single‐agent BRAFi from February 2010 to April 2015 were included in a retrospective data analysis focused on patterns of progression, treatment beyond progression (TBP) and subsequent treatments after BRAFi therapy. Analysis revealed that 51.1% of patients progressed with both new and existing metastases opposed to progression of only preexisting (28.3%) or only new (20.6%) metastases. Exclusive extracranial progression occurred in 50.6% of patients compared to both extra‐ and intracranial (29.4%) or sole cerebral progression (20%). Multivariable analyses demonstrated that single site progression and primary response to BRAFi were associated with improved progression‐free survival. Progression with exclusively new or only existing metastases and a baseline Eastern Cooperative Oncology Group (ECOG) of 0 were associated with prolonged overall survival (OS). TBP had no significant impact on OS. Other subsequent treatments showed low efficacy with the exception of anti‐PD‐1 antibodies. In conclusion we identified specific patterns of progression which significantly correlate with further prognosis after progression on BRAFi treatment. In contrast to previously published data, we could not demonstrate a significant survival benefit for BRAFi TBP. Subsequent therapies had strikingly low efficacy except for PD‐1 inhibitors. |
format | Online Article Text |
id | pubmed-5773979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57739792018-02-07 Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma Hassel, Jessica C. Buder‐Bakhaya, Kristina Bender, Carolin Zimmer, Lisa Weide, Benjamin Loquai, Carmen Ugurel, Selma Slynko, Alla Gutzmer, Ralf Cancer Med Clinical Cancer Research Despite markedly improved treatment options for metastatic melanoma, resistance to targeted therapies such as BRAF inhibitors (BRAFi) or BRAFi plus MEK inhibitors (MEKi) remains a major problem. Our aim was to characterize progression on BRAFi therapy and outcome of subsequent treatment. One hundred and eighty patients with BRAF‐mutant metastatic melanoma who had progressed on treatment with single‐agent BRAFi from February 2010 to April 2015 were included in a retrospective data analysis focused on patterns of progression, treatment beyond progression (TBP) and subsequent treatments after BRAFi therapy. Analysis revealed that 51.1% of patients progressed with both new and existing metastases opposed to progression of only preexisting (28.3%) or only new (20.6%) metastases. Exclusive extracranial progression occurred in 50.6% of patients compared to both extra‐ and intracranial (29.4%) or sole cerebral progression (20%). Multivariable analyses demonstrated that single site progression and primary response to BRAFi were associated with improved progression‐free survival. Progression with exclusively new or only existing metastases and a baseline Eastern Cooperative Oncology Group (ECOG) of 0 were associated with prolonged overall survival (OS). TBP had no significant impact on OS. Other subsequent treatments showed low efficacy with the exception of anti‐PD‐1 antibodies. In conclusion we identified specific patterns of progression which significantly correlate with further prognosis after progression on BRAFi treatment. In contrast to previously published data, we could not demonstrate a significant survival benefit for BRAFi TBP. Subsequent therapies had strikingly low efficacy except for PD‐1 inhibitors. John Wiley and Sons Inc. 2017-12-20 /pmc/articles/PMC5773979/ /pubmed/29266761 http://dx.doi.org/10.1002/cam4.1267 Text en © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Cancer Research Hassel, Jessica C. Buder‐Bakhaya, Kristina Bender, Carolin Zimmer, Lisa Weide, Benjamin Loquai, Carmen Ugurel, Selma Slynko, Alla Gutzmer, Ralf Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma |
title | Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma |
title_full | Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma |
title_fullStr | Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma |
title_full_unstemmed | Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma |
title_short | Progression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma |
title_sort | progression patterns under braf inhibitor treatment and treatment beyond progression in patients with metastatic melanoma |
topic | Clinical Cancer Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773979/ https://www.ncbi.nlm.nih.gov/pubmed/29266761 http://dx.doi.org/10.1002/cam4.1267 |
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