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Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma
Purpose/Objectives Combination BRAF (vemurafenib, dabrafenib, or encorafenib) plus MEK (trametinib, cobimetinib, or binimetinib) inhibitor therapy is now widely used in the treatment of metastatic melanoma. However, data for intracranial response to these drugs are limited. We aimed to evaluate the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cureus
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788920/ https://www.ncbi.nlm.nih.gov/pubmed/36579260 http://dx.doi.org/10.7759/cureus.31838 |
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author | Hui, Caressa Wu, Yufan (Fred) Liu, Kevin Sandhu, Navjot Blomain, Erik Binkley, Michael S Gephart, Melanie H Chang, Steven D. Li, Gordon H Reddy, Sunil A Soltys, Scott G Pollom, Erqi |
author_facet | Hui, Caressa Wu, Yufan (Fred) Liu, Kevin Sandhu, Navjot Blomain, Erik Binkley, Michael S Gephart, Melanie H Chang, Steven D. Li, Gordon H Reddy, Sunil A Soltys, Scott G Pollom, Erqi |
author_sort | Hui, Caressa |
collection | PubMed |
description | Purpose/Objectives Combination BRAF (vemurafenib, dabrafenib, or encorafenib) plus MEK (trametinib, cobimetinib, or binimetinib) inhibitor therapy is now widely used in the treatment of metastatic melanoma. However, data for intracranial response to these drugs are limited. We aimed to evaluate the intracranial efficacy of BRAF plus MEK inhibitors in patients with BRAF-mutant melanoma with brain metastases (BM) and to determine patterns of failure of these new agents to inform optimal integration of local intracranial therapy. Materials and methods We retrospectively reviewed charts of patients with BRAF-mutant melanoma with metastasis to the brain with at least one untreated brain metastasis at the time of initiation of BRAF plus MEK inhibitors at our institution from 2006 to 2020. We collected per-patient and per-lesion data on demographics, treatment modality, and outcomes. The cumulative incidence of local (LF), distant intracranial (DF), and extracranial failure (EF) were calculated with competing risk analysis with death as a competing risk and censored at the last brain MRI follow-up. LF was calculated on a per-lesion basis while DF and EF were calculated on a per-patient basis. DF was defined as any new intracranial lesions. Overall survival (OS) was analyzed using Kaplan-Meier. Logistic regression was used to identify predictors for LF. Results We identified 10 patients with 63 untreated brain metastases. The median age was 50.5 years. The median sum of the diameters of the five largest untreated brain metastases per patient was 20 mm (interquartile range 15-39 mm) and the median diameter for all measurable lesions was 4 mm. Median follow-up time was 9.0 months (range 1.4 months-46.2 months). Median OS was 13.6 months. The one-year cumulative incidence of LF, DF, and EF was 17.1%, 88.6, and 71.4%, respectively. The median time to LF, DF, and EF from the start of BRAF plus MEK inhibitors was 9.0 months, 4.7 months, and 7.0 months, respectively. The larger size of the BM was associated with LF on univariate analysis (odds ratio 1.13 per 1 mm increase in diameter, 95% confidence interval 1.019 to 1.308, p<0.02). Two (20%) patients eventually received stereotactic radiosurgery, and 2 (20%) received whole-brain radiotherapy for intracranial progression. Conclusion Although patients with BRAF-mutant melanoma with BM had fair local control on BRAF plus MEK inhibitors, the competing risk of death and distant intracranial and extracranial progression was high. Patients with larger brain metastases may benefit from local therapy. |
format | Online Article Text |
id | pubmed-9788920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cureus |
record_format | MEDLINE/PubMed |
spelling | pubmed-97889202022-12-27 Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma Hui, Caressa Wu, Yufan (Fred) Liu, Kevin Sandhu, Navjot Blomain, Erik Binkley, Michael S Gephart, Melanie H Chang, Steven D. Li, Gordon H Reddy, Sunil A Soltys, Scott G Pollom, Erqi Cureus Radiation Oncology Purpose/Objectives Combination BRAF (vemurafenib, dabrafenib, or encorafenib) plus MEK (trametinib, cobimetinib, or binimetinib) inhibitor therapy is now widely used in the treatment of metastatic melanoma. However, data for intracranial response to these drugs are limited. We aimed to evaluate the intracranial efficacy of BRAF plus MEK inhibitors in patients with BRAF-mutant melanoma with brain metastases (BM) and to determine patterns of failure of these new agents to inform optimal integration of local intracranial therapy. Materials and methods We retrospectively reviewed charts of patients with BRAF-mutant melanoma with metastasis to the brain with at least one untreated brain metastasis at the time of initiation of BRAF plus MEK inhibitors at our institution from 2006 to 2020. We collected per-patient and per-lesion data on demographics, treatment modality, and outcomes. The cumulative incidence of local (LF), distant intracranial (DF), and extracranial failure (EF) were calculated with competing risk analysis with death as a competing risk and censored at the last brain MRI follow-up. LF was calculated on a per-lesion basis while DF and EF were calculated on a per-patient basis. DF was defined as any new intracranial lesions. Overall survival (OS) was analyzed using Kaplan-Meier. Logistic regression was used to identify predictors for LF. Results We identified 10 patients with 63 untreated brain metastases. The median age was 50.5 years. The median sum of the diameters of the five largest untreated brain metastases per patient was 20 mm (interquartile range 15-39 mm) and the median diameter for all measurable lesions was 4 mm. Median follow-up time was 9.0 months (range 1.4 months-46.2 months). Median OS was 13.6 months. The one-year cumulative incidence of LF, DF, and EF was 17.1%, 88.6, and 71.4%, respectively. The median time to LF, DF, and EF from the start of BRAF plus MEK inhibitors was 9.0 months, 4.7 months, and 7.0 months, respectively. The larger size of the BM was associated with LF on univariate analysis (odds ratio 1.13 per 1 mm increase in diameter, 95% confidence interval 1.019 to 1.308, p<0.02). Two (20%) patients eventually received stereotactic radiosurgery, and 2 (20%) received whole-brain radiotherapy for intracranial progression. Conclusion Although patients with BRAF-mutant melanoma with BM had fair local control on BRAF plus MEK inhibitors, the competing risk of death and distant intracranial and extracranial progression was high. Patients with larger brain metastases may benefit from local therapy. Cureus 2022-11-23 /pmc/articles/PMC9788920/ /pubmed/36579260 http://dx.doi.org/10.7759/cureus.31838 Text en Copyright © 2022, Hui et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Radiation Oncology Hui, Caressa Wu, Yufan (Fred) Liu, Kevin Sandhu, Navjot Blomain, Erik Binkley, Michael S Gephart, Melanie H Chang, Steven D. Li, Gordon H Reddy, Sunil A Soltys, Scott G Pollom, Erqi Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma |
title | Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma |
title_full | Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma |
title_fullStr | Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma |
title_full_unstemmed | Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma |
title_short | Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma |
title_sort | intracranial control with combination braf and mek inhibitor therapy in patients with metastatic melanoma |
topic | Radiation Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788920/ https://www.ncbi.nlm.nih.gov/pubmed/36579260 http://dx.doi.org/10.7759/cureus.31838 |
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