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Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis

PURPOSE: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signa...

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Autores principales: Luger, Anna-Luisa, König, Sven, Samp, Patrick Felix, Urban, Hans, Divé, Iris, Burger, Michael C., Voss, Martin, Franz, Kea, Fokas, Emmanouil, Filipski, Katharina, Demes, Melanie-Christin, Stenzinger, Albrecht, Sahm, Felix, Reuss, David E., Harter, Patrick N., Wagner, Sebastian, Hattingen, Elke, Wichert, Jennifer, Lapa, Constantin, Fröhling, Stefan, Steinbach, Joachim P., Ronellenfitsch, Michael W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424147/
https://www.ncbi.nlm.nih.gov/pubmed/35864412
http://dx.doi.org/10.1007/s11060-022-04049-w
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author Luger, Anna-Luisa
König, Sven
Samp, Patrick Felix
Urban, Hans
Divé, Iris
Burger, Michael C.
Voss, Martin
Franz, Kea
Fokas, Emmanouil
Filipski, Katharina
Demes, Melanie-Christin
Stenzinger, Albrecht
Sahm, Felix
Reuss, David E.
Harter, Patrick N.
Wagner, Sebastian
Hattingen, Elke
Wichert, Jennifer
Lapa, Constantin
Fröhling, Stefan
Steinbach, Joachim P.
Ronellenfitsch, Michael W.
author_facet Luger, Anna-Luisa
König, Sven
Samp, Patrick Felix
Urban, Hans
Divé, Iris
Burger, Michael C.
Voss, Martin
Franz, Kea
Fokas, Emmanouil
Filipski, Katharina
Demes, Melanie-Christin
Stenzinger, Albrecht
Sahm, Felix
Reuss, David E.
Harter, Patrick N.
Wagner, Sebastian
Hattingen, Elke
Wichert, Jennifer
Lapa, Constantin
Fröhling, Stefan
Steinbach, Joachim P.
Ronellenfitsch, Michael W.
author_sort Luger, Anna-Luisa
collection PubMed
description PURPOSE: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy. METHODS: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected. RESULTS: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI. CONCLUSION: A broad range of actionable alterations was targeted with available molecular therapeutics. However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-022-04049-w.
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spelling pubmed-94241472022-08-31 Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis Luger, Anna-Luisa König, Sven Samp, Patrick Felix Urban, Hans Divé, Iris Burger, Michael C. Voss, Martin Franz, Kea Fokas, Emmanouil Filipski, Katharina Demes, Melanie-Christin Stenzinger, Albrecht Sahm, Felix Reuss, David E. Harter, Patrick N. Wagner, Sebastian Hattingen, Elke Wichert, Jennifer Lapa, Constantin Fröhling, Stefan Steinbach, Joachim P. Ronellenfitsch, Michael W. J Neurooncol Research PURPOSE: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy. METHODS: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected. RESULTS: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI. CONCLUSION: A broad range of actionable alterations was targeted with available molecular therapeutics. However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-022-04049-w. Springer US 2022-07-21 2022 /pmc/articles/PMC9424147/ /pubmed/35864412 http://dx.doi.org/10.1007/s11060-022-04049-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Luger, Anna-Luisa
König, Sven
Samp, Patrick Felix
Urban, Hans
Divé, Iris
Burger, Michael C.
Voss, Martin
Franz, Kea
Fokas, Emmanouil
Filipski, Katharina
Demes, Melanie-Christin
Stenzinger, Albrecht
Sahm, Felix
Reuss, David E.
Harter, Patrick N.
Wagner, Sebastian
Hattingen, Elke
Wichert, Jennifer
Lapa, Constantin
Fröhling, Stefan
Steinbach, Joachim P.
Ronellenfitsch, Michael W.
Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
title Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
title_full Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
title_fullStr Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
title_full_unstemmed Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
title_short Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
title_sort molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424147/
https://www.ncbi.nlm.nih.gov/pubmed/35864412
http://dx.doi.org/10.1007/s11060-022-04049-w
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