TY  - JOUR
A1  - Luger, Anna-Luisa
A1  - König, Sven
A1  - Samp, Patrick Felix
A1  - Urban, Hans
A1  - Divé, Iris
A1  - Burger, Michael Christian
A1  - Voß, Martin
A1  - Franz, Kea
A1  - Fokas, Emmanouil
A1  - Filipski, Katharina Johanna
A1  - Demes, Melanie Christin
A1  - Stenzinger, Albrecht
A1  - Sahm, Felix
A1  - Reuss, David
A1  - Harter, Patrick Nikolaus
A1  - Wagner, Sebastian
A1  - Hattingen, Elke
A1  - Wichert, Jennifer
A1  - Lapa, Constantin Frederik Victor
A1  - Fröhling, Stefan
A1  - Steinbach, Joachim Peter
A1  - Ronellenfitsch, Michael Wilfried
T1  - Molecular matched targeted therapies for primary brain tumors - a single center retrospective analysis
T2  - Journal of neuro-oncology
N2  - 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.
KW  - Brain tumor
KW  - Glioma
KW  - Molecular matched therapy
KW  - Targeted therapy
KW  - Molecular profiling
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69467
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-694670
SN  - 1573-7373
N1  - Open Access funding enabled and organized by Projekt DEAL.
N1  - The Dr. Senckenberg Foundation supports the Dr. Senckenberg Institute of Neurooncology.
VL  - 159
IS  - 2
SP  - 243
EP  - 259
PB  - Springer Science + Business Media B.V
CY  - Dordrecht [u.a.]
ER  -