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THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES

BACKGROUND: BRAF mutations occur in 50% of melanoma patients. Targeted agents – BRAF and MEK inhibitors and immunotherapy improve survival of melanoma patients with BRAF mutations. These agents have intracranial efficacy as shown in clinical trials. However, the efficacy of immunotherapies (immune c...

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Autores principales: Lauko, Adam, Sagar, Soumya, Barnett, Addison, Wei, Wei, Chao, Samuel, Stevens, Glen, Peereboom, David, Yu, Jennifer, Murphy, Erin, Angelov, Lilyana, Mohammadi, Alireza, Suh, John, Barnett, Gene, Ahluwalia, Manmeet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213464/
http://dx.doi.org/10.1093/noajnl/vdz014.053
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author Lauko, Adam
Sagar, Soumya
Barnett, Addison
Wei, Wei
Chao, Samuel
Stevens, Glen
Peereboom, David
Yu, Jennifer
Murphy, Erin
Angelov, Lilyana
Mohammadi, Alireza
Suh, John
Barnett, Gene
Ahluwalia, Manmeet
author_facet Lauko, Adam
Sagar, Soumya
Barnett, Addison
Wei, Wei
Chao, Samuel
Stevens, Glen
Peereboom, David
Yu, Jennifer
Murphy, Erin
Angelov, Lilyana
Mohammadi, Alireza
Suh, John
Barnett, Gene
Ahluwalia, Manmeet
author_sort Lauko, Adam
collection PubMed
description BACKGROUND: BRAF mutations occur in 50% of melanoma patients. Targeted agents – BRAF and MEK inhibitors and immunotherapy improve survival of melanoma patients with BRAF mutations. These agents have intracranial efficacy as shown in clinical trials. However, the efficacy of immunotherapies (immune checkpoint blockade) in melanoma brain metastases and the correlation with BRAF status is not as well characterized. METHODS: We reviewed 351 patients with melanoma brain metastases treated at our tertiary care center between 2000 and 2018, 75 of which received immunotherapy with known BRAF mutational status. Two-year, 5-year, and median overall survival (OS) was calculated from the start of immunotherapy to compare the efficacy of immunotherapy in BRAF mutant and BRAF wild type patients using the log-rank test. RESULTS: At the time of diagnosis of brain metastasis, the median age was 61 (23–87) years, median KPS was 80 (50–100), number of intracranial lesions was 2 (1–15), and 79% had extra-cranial metastases. Sixty-three patients were treated with stereotactic radiosurgery (SRS), 27 underwent whole brain radiation (WBRT) and 21 underwent surgery. When treated with immunotherapy, BRAF mutant and BRAF wild type median survival was 15.7 months (95% CI=9.4 – 42.4) and 6.9 (95% CI=4.1– 26.7) months (p-value=0.205), respectively. Two-year BRAF mutant and BRAF wild type survival was 35% (95% CI=21 – 58) and 28% (95% CI=16 – 51), and 5-year survival was 22% (95% CI=10 – 46) and 23% (95% CI=11 – 47), respectively. CONCLUSIONS: Twenty percent of patients with BRAF mutant and BRAF wild-type patients treated with immunotherapy derive a long-term benefit from immunotherapy and multimodality treatment and are alive 5 years from diagnosis of brain metastases. This was rarely seen in the pre-immunotherapy era in melanoma brain metastases. There was no difference in outcome based on the BRAF mutational status with use of immunotherapy in melanoma brain metastases.
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spelling pubmed-72134642020-07-07 THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES Lauko, Adam Sagar, Soumya Barnett, Addison Wei, Wei Chao, Samuel Stevens, Glen Peereboom, David Yu, Jennifer Murphy, Erin Angelov, Lilyana Mohammadi, Alireza Suh, John Barnett, Gene Ahluwalia, Manmeet Neurooncol Adv Abstracts BACKGROUND: BRAF mutations occur in 50% of melanoma patients. Targeted agents – BRAF and MEK inhibitors and immunotherapy improve survival of melanoma patients with BRAF mutations. These agents have intracranial efficacy as shown in clinical trials. However, the efficacy of immunotherapies (immune checkpoint blockade) in melanoma brain metastases and the correlation with BRAF status is not as well characterized. METHODS: We reviewed 351 patients with melanoma brain metastases treated at our tertiary care center between 2000 and 2018, 75 of which received immunotherapy with known BRAF mutational status. Two-year, 5-year, and median overall survival (OS) was calculated from the start of immunotherapy to compare the efficacy of immunotherapy in BRAF mutant and BRAF wild type patients using the log-rank test. RESULTS: At the time of diagnosis of brain metastasis, the median age was 61 (23–87) years, median KPS was 80 (50–100), number of intracranial lesions was 2 (1–15), and 79% had extra-cranial metastases. Sixty-three patients were treated with stereotactic radiosurgery (SRS), 27 underwent whole brain radiation (WBRT) and 21 underwent surgery. When treated with immunotherapy, BRAF mutant and BRAF wild type median survival was 15.7 months (95% CI=9.4 – 42.4) and 6.9 (95% CI=4.1– 26.7) months (p-value=0.205), respectively. Two-year BRAF mutant and BRAF wild type survival was 35% (95% CI=21 – 58) and 28% (95% CI=16 – 51), and 5-year survival was 22% (95% CI=10 – 46) and 23% (95% CI=11 – 47), respectively. CONCLUSIONS: Twenty percent of patients with BRAF mutant and BRAF wild-type patients treated with immunotherapy derive a long-term benefit from immunotherapy and multimodality treatment and are alive 5 years from diagnosis of brain metastases. This was rarely seen in the pre-immunotherapy era in melanoma brain metastases. There was no difference in outcome based on the BRAF mutational status with use of immunotherapy in melanoma brain metastases. Oxford University Press 2019-08-12 /pmc/articles/PMC7213464/ http://dx.doi.org/10.1093/noajnl/vdz014.053 Text en © The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Lauko, Adam
Sagar, Soumya
Barnett, Addison
Wei, Wei
Chao, Samuel
Stevens, Glen
Peereboom, David
Yu, Jennifer
Murphy, Erin
Angelov, Lilyana
Mohammadi, Alireza
Suh, John
Barnett, Gene
Ahluwalia, Manmeet
THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES
title THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES
title_full THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES
title_fullStr THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES
title_full_unstemmed THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES
title_short THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES
title_sort ther-10. impact of braf mutational status on the efficacy of immunotherapy for melanoma brain metastases
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213464/
http://dx.doi.org/10.1093/noajnl/vdz014.053
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