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Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients

Fibroblast growth factor receptor (FGFR) genomic alterations (GAs) represent an actionable target, key to the pathogenesis of some urothelial cancers (UCs). Though FGFR GAs are common in noninvasive UC, little is known about their role in the metastatic(m) setting and response to therapy. This study...

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Autores principales: Sevillano Fernández, Elena, Madurga de Lacalle, Rodrigo, Rodriguez Moreno, Juan Francisco, Barquín García, Arantzazu, Yagüe Fernández, Mónica, Navarro Alcaraz, Paloma, Barba Llacer, María, Quiralte Pulido, Miguel, García-Donás Jiménez, Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369263/
https://www.ncbi.nlm.nih.gov/pubmed/35956100
http://dx.doi.org/10.3390/jcm11154483
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author Sevillano Fernández, Elena
Madurga de Lacalle, Rodrigo
Rodriguez Moreno, Juan Francisco
Barquín García, Arantzazu
Yagüe Fernández, Mónica
Navarro Alcaraz, Paloma
Barba Llacer, María
Quiralte Pulido, Miguel
García-Donás Jiménez, Jesús
author_facet Sevillano Fernández, Elena
Madurga de Lacalle, Rodrigo
Rodriguez Moreno, Juan Francisco
Barquín García, Arantzazu
Yagüe Fernández, Mónica
Navarro Alcaraz, Paloma
Barba Llacer, María
Quiralte Pulido, Miguel
García-Donás Jiménez, Jesús
author_sort Sevillano Fernández, Elena
collection PubMed
description Fibroblast growth factor receptor (FGFR) genomic alterations (GAs) represent an actionable target, key to the pathogenesis of some urothelial cancers (UCs). Though FGFR GAs are common in noninvasive UC, little is known about their role in the metastatic(m) setting and response to therapy. This study aimed to assess the impact of FGFR alterations on sensitivity to systemic treatments and survival and to validate Bajorin’s and Bellmunt’s prognostic scores in mUC patients according to their FGFR status. We retrospectively analyzed data from 98 patients with tumor-sequenced UC who received treatment between January 2010 and December 2020. Up to 77 developed metastatic disease and were deemed the study population. Twenty-six showed FGFR GAs. A trend toward a better response to cisplatin and checkpoint inhibitors was suggested favoring FGFR GA tumors. FGFR GA patients who received an FGFR inhibitor as first-line had poorer responses compared with other options (20% vs. 68.4%, p = 0.0065). Median PFS was 6 vs. 5 months in the FGFR GA vs. FGFR WT cohort (p = 0.71). Median OS was significantly worse in the FGFR GA vs. FGFR WT cohort (16.2 vs. 31.9 months, p = 0.045). Multivariate analyses deemed FGFR GAs as a factor independently associated with the outcome (HR 2.59 (95% CI 1.21–5.55)). Bajorin’s model correctly predicted clinical outcomes in the whole study population but not in FGFR GA cases. FGFR GAs are a relevant biomarker in mUC that could condition the response to systemic therapy. New prognostic models, including this molecular determination, should be designed and validated.
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spelling pubmed-93692632022-08-12 Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients Sevillano Fernández, Elena Madurga de Lacalle, Rodrigo Rodriguez Moreno, Juan Francisco Barquín García, Arantzazu Yagüe Fernández, Mónica Navarro Alcaraz, Paloma Barba Llacer, María Quiralte Pulido, Miguel García-Donás Jiménez, Jesús J Clin Med Article Fibroblast growth factor receptor (FGFR) genomic alterations (GAs) represent an actionable target, key to the pathogenesis of some urothelial cancers (UCs). Though FGFR GAs are common in noninvasive UC, little is known about their role in the metastatic(m) setting and response to therapy. This study aimed to assess the impact of FGFR alterations on sensitivity to systemic treatments and survival and to validate Bajorin’s and Bellmunt’s prognostic scores in mUC patients according to their FGFR status. We retrospectively analyzed data from 98 patients with tumor-sequenced UC who received treatment between January 2010 and December 2020. Up to 77 developed metastatic disease and were deemed the study population. Twenty-six showed FGFR GAs. A trend toward a better response to cisplatin and checkpoint inhibitors was suggested favoring FGFR GA tumors. FGFR GA patients who received an FGFR inhibitor as first-line had poorer responses compared with other options (20% vs. 68.4%, p = 0.0065). Median PFS was 6 vs. 5 months in the FGFR GA vs. FGFR WT cohort (p = 0.71). Median OS was significantly worse in the FGFR GA vs. FGFR WT cohort (16.2 vs. 31.9 months, p = 0.045). Multivariate analyses deemed FGFR GAs as a factor independently associated with the outcome (HR 2.59 (95% CI 1.21–5.55)). Bajorin’s model correctly predicted clinical outcomes in the whole study population but not in FGFR GA cases. FGFR GAs are a relevant biomarker in mUC that could condition the response to systemic therapy. New prognostic models, including this molecular determination, should be designed and validated. MDPI 2022-08-01 /pmc/articles/PMC9369263/ /pubmed/35956100 http://dx.doi.org/10.3390/jcm11154483 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sevillano Fernández, Elena
Madurga de Lacalle, Rodrigo
Rodriguez Moreno, Juan Francisco
Barquín García, Arantzazu
Yagüe Fernández, Mónica
Navarro Alcaraz, Paloma
Barba Llacer, María
Quiralte Pulido, Miguel
García-Donás Jiménez, Jesús
Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients
title Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients
title_full Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients
title_fullStr Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients
title_full_unstemmed Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients
title_short Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients
title_sort prognostic value and clinical significance of fgfr genomic alterations (gas) in metastatic urothelial cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369263/
https://www.ncbi.nlm.nih.gov/pubmed/35956100
http://dx.doi.org/10.3390/jcm11154483
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