Efficacy of BRAF and MEK Inhibition in Patients with BRAF-Mutant Advanced Melanoma and Germline CDKN2A Pathogenic Variants.
BRAF inhibitors
CDKN2A
MEK inhibitors
genetic counseling
melanoma
melanoma susceptibility
targeted therapy
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
18 May 2021
18 May 2021
Historique:
received:
18
04
2021
revised:
09
05
2021
accepted:
15
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
3
6
2021
Statut:
epublish
Résumé
Inherited pathogenic variants (PVs) in the CDKN2A tumor suppressor gene are among the strongest risk factors for cutaneous melanoma. Dysregulation of the p16/RB1 pathway may intrinsically limit the activity of MAPK-directed therapy due to the interplay between the two pathways. In our study, we assessed, for the first time, whether patients with germline CDKN2A PVs achieve suboptimal results with BRAF inhibitors (BRAFi)+/-MEK inhibitors (MEKi). We compared the response rate of nineteen CDKN2A PVs carriers who received first-line treatment with BRAFi+/-MEKi with an expected rate derived from phase III trials and "real-world" studies. We observed partial response in 16/19 patients (84%), and no complete responses. The overall response rate was higher than that expected from phase III trials (66%), although not statistically significant (
Identifiants
pubmed: 34069952
pii: cancers13102440
doi: 10.3390/cancers13102440
pmc: PMC8157545
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Italian Ministry of Health
ID : RF-2016-02362288
Organisme : IRCCS Ospedale Policlinico San Martino
ID : Ricerca Corrente
Organisme : University of Genoa
ID : FRA 2017-2019
Organisme : Italian Association for Cancer Research
ID : IG15460
Organisme : Swedish Cancer society
ID : CAN 2017/503
Organisme : The Cancer Research Funds of Radiumhemmet
ID : 194092
Références
J Natl Cancer Inst. 2016 Jun 10;108(11):
pubmed: 27287845
J Med Genet. 2018 Oct;55(10):661-668
pubmed: 29661971
J Am Acad Dermatol. 2016 Feb;74(2):325-32
pubmed: 26775776
Nat Commun. 2017 Nov 23;8(1):1738
pubmed: 29170503
J Med Genet. 2007 Feb;44(2):99-106
pubmed: 16905682
J Med Genet. 2020 May;57(5):316-321
pubmed: 30291219
J Invest Dermatol. 2014 Dec;134(12):3000-3003
pubmed: 24999598
J Med Genet. 2014 Aug;51(8):545-52
pubmed: 24935963
Nature. 2002 Jun 27;417(6892):949-54
pubmed: 12068308
J Am Acad Dermatol. 2019 May;80(5):1263-1271
pubmed: 30274933
J Clin Oncol. 2005 May 1;23(13):3043-51
pubmed: 15860862
J Invest Dermatol. 2014 Jan;134(1):287-290
pubmed: 23771122
Hered Cancer Clin Pract. 2014 Nov 20;12(1):20
pubmed: 25780468
Clin Cancer Res. 2013 Sep 1;19(17):4868-78
pubmed: 23833299
J Am Acad Dermatol. 2009 Nov;61(5):775-82
pubmed: 19500876
Mol Cancer Ther. 2008 Sep;7(9):2876-83
pubmed: 18790768
Front Mol Biosci. 2020 Jul 14;7:154
pubmed: 32760738
N Engl J Med. 2019 Aug 15;381(7):626-636
pubmed: 31166680