Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial.
Decision-making
Molecular profiling
Precision medicine
Primary brain tumor
Targeted therapy
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
05 Nov 2021
05 Nov 2021
Historique:
received:
23
12
2020
accepted:
15
06
2021
entrez:
5
11
2021
pubmed:
6
11
2021
medline:
1
3
2022
Statut:
epublish
Résumé
Immunohistochemistry and recent molecular technologies progressively guided access to personalized anti-tumoral therapies. We explored the feasibility, efficacy, and the impact of molecular profiling in patients with advanced brain tumors. This multicentric prospective trial ProfiLER enrolled patients with primary brain tumors, who have been pre-treated with at least one line of anti-cancer treatment, and for whom molecular profiles had been achieved using next-generation sequencing and/or comparative genomic hybridization on fresh or archived samples from tumor, relapse, or biopsies. A molecular tumor board weekly analyzed results and proposed molecular-based recommended therapy (MBRT). From February 2013 to December 2015, we enrolled 141 patients with primary brain tumor and analyzed 105 patients for whom tumor genomic profiles had been achieved. Histology mainly identified glioblastoma (N = 46, 44%), low-grade glioma (N = 26, 25%), high-grade glioma (N = 12, 11%), and atypical and anaplastic meningioma (N = 8, 8%). Forty-three (41%) patients presented at least one actionable molecular alteration. Out of 61 alterations identified, the most frequent alterations occurred in CDKN2A (N = 18), EGFR (N = 12), PDGFRa (N = 8), PTEN (N = 8), CDK4 (N = 7), KIT (N = 6), PIK3CA (N = 5), and MDM2 (N = 3). Sixteen (15%) patients could not be proposed for a MBRT due to early death (N = 5), lack of available clinical trials (N = 9), or inappropriate results (N = 2). Only six (6%) of the 27 (26%) patients for whom a MBRT had been proposed finally initiated MBRT (everolimus (N = 3), erlotinib (N = 1), ruxolitinib (N = 1), and sorafenib (N = 1)), but discontinued treatment for toxicity (N = 4) or clinical progression (N = 2). High-throughput sequencing in patients with brain tumors may be routinely performed, especially when macroscopic surgery samples are available; nevertheless delays should be reduced. Criteria for clinical trial enrollment should be reconsidered in patients with brain tumors, and a panel of genes specifically dedicated to neurologic tumors should be developed to help decision-making in clinical practice.
Identifiants
pubmed: 34739635
doi: 10.1007/s12032-021-01536-4
pii: 10.1007/s12032-021-01536-4
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
4Subventions
Organisme : Institut National Du Cancer
ID : DGOS-INCA-46644
Organisme : BPI financement European community
ID : E8983-PREDICTIV
Organisme : Agence national de la recherche
ID : ANR Labex DEvweCAN 10-LABX-0061
Organisme : European Commission
ID : EURACAN 739521
Informations de copyright
© 2021. Springer Science+Business Media, LLC, part of Springer Nature.
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