Dual BRAF/MEK blockade restores CNS responses in BRAF-mutant Erdheim-Chester disease patients following BRAF inhibitor monotherapy.
BRAF
Cobimetinib
Erdheim–Chester disease
Vemurafenib
histiocytosis
Journal
Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003
Informations de publication
Date de publication:
Historique:
entrez:
10
7
2020
pubmed:
10
7
2020
medline:
10
7
2020
Statut:
epublish
Résumé
Erdheim-Chester disease (ECD), a rare inflammatory myeloid neoplasm, is known to be fundamentally reliant on the constitutive activation of the MAPK signaling pathway in the majority of patients. Consequently, inhibition of the V600E-mutant BRAF kinase has proven to be a safe and efficacious long-term therapeutic strategy for We retrospectively describe 3 Three patients with a mean age of 52.6 years were treated with Vemurafenib for a mean duration of 26.6 months (range: 6-52). Monotherapies were upgraded to Vemurafenib/Cobimetinib dual therapy. The combination therapy was administered for a mean duration of 21 months (range: 19-23). All patients exhibited clinical and neurological improvement. Regression of lesions on MRI was noted in 2 patients. Both patients characterized by a PET-avid disease responded to the biological treatment regimen with complete metabolic remissions. Dual inhibition of BRAF and downstream MEK may be a safe and effective therapeutic strategy for
Sections du résumé
BACKGROUND
BACKGROUND
Erdheim-Chester disease (ECD), a rare inflammatory myeloid neoplasm, is known to be fundamentally reliant on the constitutive activation of the MAPK signaling pathway in the majority of patients. Consequently, inhibition of the V600E-mutant BRAF kinase has proven to be a safe and efficacious long-term therapeutic strategy for
METHODS
METHODS
We retrospectively describe 3
RESULTS
RESULTS
Three patients with a mean age of 52.6 years were treated with Vemurafenib for a mean duration of 26.6 months (range: 6-52). Monotherapies were upgraded to Vemurafenib/Cobimetinib dual therapy. The combination therapy was administered for a mean duration of 21 months (range: 19-23). All patients exhibited clinical and neurological improvement. Regression of lesions on MRI was noted in 2 patients. Both patients characterized by a PET-avid disease responded to the biological treatment regimen with complete metabolic remissions.
CONCLUSION
CONCLUSIONS
Dual inhibition of BRAF and downstream MEK may be a safe and effective therapeutic strategy for
Identifiants
pubmed: 32642685
doi: 10.1093/noajnl/vdaa024
pii: vdaa024
pmc: PMC7212923
doi:
Types de publication
Journal Article
Langues
eng
Pagination
vdaa024Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201247
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
Références
Nat Rev Clin Oncol. 2013 Jul;10(7):390-9
pubmed: 23712190
Eur J Cancer. 2017 Jul;79:176-184
pubmed: 28501764
Cancer Res. 2016 Mar 15;76(6):1476-84
pubmed: 26825172
Haematologica. 2018 Apr;103(4):e177-e180
pubmed: 29472347
Blood. 2016 Mar 17;127(11):1509-12
pubmed: 26847247
Nature. 2011 Nov 23;480(7377):387-90
pubmed: 22113612
J Invest Dermatol. 2015 Dec;135(12):2913-2918
pubmed: 26569584
Blood. 2013 Feb 28;121(9):1495-500
pubmed: 23258922
N Engl J Med. 2015 Jan 1;372(1):30-9
pubmed: 25399551
Cell Res. 2002 Mar;12(1):9-18
pubmed: 11942415
Orphanet J Rare Dis. 2013 Sep 08;8:137
pubmed: 24011030
Cancer Cell. 2012 Nov 13;22(5):668-82
pubmed: 23153539
Blood. 2011 Mar 10;117(10):2778-82
pubmed: 21239701
Cancer Discov. 2018 Sep;8(9):1130-1141
pubmed: 29880583
Oncologist. 2018 Dec;23(12):1520-1524
pubmed: 30120160
Oncotarget. 2016 May 24;7(21):30907-23
pubmed: 27127178
Cancer Res. 2014 Dec 1;74(23):7079-89
pubmed: 25320010
N Engl J Med. 2012 Dec 13;367(24):2316-21
pubmed: 23134356
Semin Arthritis Rheum. 2012 Jun;41(6):907-13
pubmed: 22300602
Medicine (Baltimore). 1996 May;75(3):157-69
pubmed: 8965684
Nature. 2010 Dec 16;468(7326):973-7
pubmed: 21107323
J Clin Oncol. 2012 Oct 1;30(28):e286-90
pubmed: 22869874
J Pharmacol Exp Ther. 2013 Mar;344(3):655-64
pubmed: 23249624
Blood. 2014 Jul 24;124(4):483-92
pubmed: 24850756
Cancer Discov. 2016 Feb;6(2):154-65
pubmed: 26566875
Cancer Treat Rev. 2013 Dec;39(8):833-8
pubmed: 23845462
N Engl J Med. 2015 Aug 20;373(8):726-36
pubmed: 26287849
J Natl Compr Canc Netw. 2018 Jan;16(1):4-10
pubmed: 29295876
Cancer Discov. 2014 Jan;4(1):27-30
pubmed: 24402945
Nat Med. 2016 Sep;22(9):1056-61
pubmed: 27500726
Am J Ophthalmol. 2001 Dec;132(6):945-7
pubmed: 11730673
Nature. 2010 Mar 18;464(7287):427-30
pubmed: 20179705
Nature. 2010 Dec 16;468(7326):968-72
pubmed: 21107320
Br J Dermatol. 2016 May;174(5):1159-60
pubmed: 26853702
Cancer Discov. 2014 Jan;4(1):80-93
pubmed: 24265155
Blood. 2011 Mar 10;117(10):2783-90
pubmed: 21205927
Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618767611
pubmed: 29595366
Br J Haematol. 2018 Jan;180(1):150-153
pubmed: 27711968
Cancer Discov. 2014 Jan;4(1):61-8
pubmed: 24265154
Blood. 2012 Sep 27;120(13):2700-3
pubmed: 22879539
Blood. 2017 Sep 14;130(11):1377-1380
pubmed: 28667012
J Clin Oncol. 2015 Feb 10;33(5):411-8
pubmed: 25422482
Cancer Cell. 2010 Dec 14;18(6):683-95
pubmed: 21156289
Expert Rev Clin Immunol. 2015;11(9):1033-42
pubmed: 26197238
N Engl J Med. 2012 Jan 19;366(3):207-15
pubmed: 22256804
Expert Opin Pharmacother. 2014 Apr;15(5):589-92
pubmed: 24456413
N Engl J Med. 2014 Nov 13;371(20):1877-88
pubmed: 25265492
Ann Rheum Dis. 2015 Aug;74(8):1596-602
pubmed: 24671772
N Engl J Med. 2014 Nov 13;371(20):1867-76
pubmed: 25265494