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Successful treatment with avapritinib in patient with mucosal metastatic melanoma

Metastatic vulvar melanoma is a rare and aggressive disease and survival is usually poor. Vulvar melanomas harbor BRAF V600 mutations only infrequently; consequently, target therapy is a rare therapeutic option and immunotherapy usually has only a weak effect. On the other hand, KIT mutations are ra...

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Autores principales: Cocorocchio, Emilia, Pala, Laura, Conforti, Fabio, Guerini-Rocco, Elena, De Pas, Tommaso, Ferrucci, Pier Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406922/
https://www.ncbi.nlm.nih.gov/pubmed/32821296
http://dx.doi.org/10.1177/1758835920946158
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author Cocorocchio, Emilia
Pala, Laura
Conforti, Fabio
Guerini-Rocco, Elena
De Pas, Tommaso
Ferrucci, Pier Francesco
author_facet Cocorocchio, Emilia
Pala, Laura
Conforti, Fabio
Guerini-Rocco, Elena
De Pas, Tommaso
Ferrucci, Pier Francesco
author_sort Cocorocchio, Emilia
collection PubMed
description Metastatic vulvar melanoma is a rare and aggressive disease and survival is usually poor. Vulvar melanomas harbor BRAF V600 mutations only infrequently; consequently, target therapy is a rare therapeutic option and immunotherapy usually has only a weak effect. On the other hand, KIT mutations are rare in cutaneous melanomas, but relatively frequent in mucosal melanomas, particularly in vulvar-vaginal melanomas, and can be a therapeutic target. Herein, we report a clinical case of a patient with metastatic vulvar melanoma, harboring an exon 17 c-KIT mutation, treated with avapritinib (BLU-285) – a highly potent and selective oral kinase inhibitor designed to treat imatinib-resistant gastro-intestinal stromal tumors (GIST) by targeting KIT/PDGFRα activation loop mutants (exons 17/18). After failure of the combination of ipilimumab + nivolumab first and then nivolumab alone, the patient received avapritinib 300 mg/daily for central nervous system (CNS), lymph-nodal, right adrenal gland, lung, and subcutaneous metastases. Best response was partial remission, according to RECIST 1.1 criteria. Time to treatment progression was 11 months. Main toxicities were grade 2 cutaneous vasculitis that required avapritinib discontinuation, and grade 2 uveitis of unknown origin, treated by vitrectomy and empiric antibiotic and antiviral therapy due to negative cultural tests. Uveitis was detected at the time of progression and therapy was definitively discontinued. In conclusion, avapritinib proved to be effective even in the presence of a pretreated disease, a high tumor burden, and brain metastases. In our experience, treatment was feasible and toxicity manageable. Considering the lack of effective therapies and the poor outcome of the disease, determination of c-KIT mutations should be performed routinely in cases of metastatic mucosal melanoma.
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spelling pubmed-74069222020-08-19 Successful treatment with avapritinib in patient with mucosal metastatic melanoma Cocorocchio, Emilia Pala, Laura Conforti, Fabio Guerini-Rocco, Elena De Pas, Tommaso Ferrucci, Pier Francesco Ther Adv Med Oncol Case Report Metastatic vulvar melanoma is a rare and aggressive disease and survival is usually poor. Vulvar melanomas harbor BRAF V600 mutations only infrequently; consequently, target therapy is a rare therapeutic option and immunotherapy usually has only a weak effect. On the other hand, KIT mutations are rare in cutaneous melanomas, but relatively frequent in mucosal melanomas, particularly in vulvar-vaginal melanomas, and can be a therapeutic target. Herein, we report a clinical case of a patient with metastatic vulvar melanoma, harboring an exon 17 c-KIT mutation, treated with avapritinib (BLU-285) – a highly potent and selective oral kinase inhibitor designed to treat imatinib-resistant gastro-intestinal stromal tumors (GIST) by targeting KIT/PDGFRα activation loop mutants (exons 17/18). After failure of the combination of ipilimumab + nivolumab first and then nivolumab alone, the patient received avapritinib 300 mg/daily for central nervous system (CNS), lymph-nodal, right adrenal gland, lung, and subcutaneous metastases. Best response was partial remission, according to RECIST 1.1 criteria. Time to treatment progression was 11 months. Main toxicities were grade 2 cutaneous vasculitis that required avapritinib discontinuation, and grade 2 uveitis of unknown origin, treated by vitrectomy and empiric antibiotic and antiviral therapy due to negative cultural tests. Uveitis was detected at the time of progression and therapy was definitively discontinued. In conclusion, avapritinib proved to be effective even in the presence of a pretreated disease, a high tumor burden, and brain metastases. In our experience, treatment was feasible and toxicity manageable. Considering the lack of effective therapies and the poor outcome of the disease, determination of c-KIT mutations should be performed routinely in cases of metastatic mucosal melanoma. SAGE Publications 2020-07-31 /pmc/articles/PMC7406922/ /pubmed/32821296 http://dx.doi.org/10.1177/1758835920946158 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Case Report
Cocorocchio, Emilia
Pala, Laura
Conforti, Fabio
Guerini-Rocco, Elena
De Pas, Tommaso
Ferrucci, Pier Francesco
Successful treatment with avapritinib in patient with mucosal metastatic melanoma
title Successful treatment with avapritinib in patient with mucosal metastatic melanoma
title_full Successful treatment with avapritinib in patient with mucosal metastatic melanoma
title_fullStr Successful treatment with avapritinib in patient with mucosal metastatic melanoma
title_full_unstemmed Successful treatment with avapritinib in patient with mucosal metastatic melanoma
title_short Successful treatment with avapritinib in patient with mucosal metastatic melanoma
title_sort successful treatment with avapritinib in patient with mucosal metastatic melanoma
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406922/
https://www.ncbi.nlm.nih.gov/pubmed/32821296
http://dx.doi.org/10.1177/1758835920946158
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