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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...

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Autores principales: Hassel, Jessica C., Buder‐Bakhaya, Kristina, Bender, Carolin, Zimmer, Lisa, Weide, Benjamin, Loquai, Carmen, Ugurel, Selma, Slynko, Alla, Gutzmer, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
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.
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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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