Efficacy of systemic therapies in men with metastatic castration resistant prostate cancer harboring germline ATM versus BRCA2 mutations.
Androstenes
/ therapeutic use
Antineoplastic Agents
/ therapeutic use
Ataxia Telangiectasia Mutated Proteins
/ genetics
BRCA2 Protein
/ genetics
Benzamides
/ therapeutic use
Docetaxel
/ therapeutic use
Germ-Line Mutation
Humans
Male
Medication Therapy Management
/ standards
Middle Aged
Neoplasm Grading
Neoplasm Staging
Nitriles
/ therapeutic use
Patient Selection
Phenylthiohydantoin
/ therapeutic use
Poly(ADP-ribose) Polymerase Inhibitors
/ therapeutic use
Prostate-Specific Antigen
/ blood
Prostatic Neoplasms, Castration-Resistant
/ genetics
Retrospective Studies
Survival Analysis
ATM
BRCA2
PARPi
abiraterone
docetaxel
enzalutamide
germline
homologous recombination deficiency
platinum
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
24
06
2021
accepted:
30
08
2021
pubmed:
14
9
2021
medline:
22
2
2022
entrez:
13
9
2021
Statut:
ppublish
Résumé
Among men with metastatic prostate cancer, about 10% have germline alterations in DNA damage response genes. Most studies have examined BRCA2 alone or an aggregate of BRCA1/2 and ATM. Emerging data suggest that ATM mutations may have distinct biology and warrant individual evaluation. The objective of this study is to determine whether response to prostate cancer systemic therapies differs between men with germline mutations in ATM (gATM) and BRCA2 (gBRCA2). This is an international multicenter retrospective matched cohort study of men with prostate cancer harboring gATM or gBRCA2. PSA The study included 45 gATM and 45 gBRCA2 patients, matched on stage and year of germline testing. Patients with gATM and gBRCA2 had similar age, Gleason grade, and PSA at diagnosis. We did not observe differences in PSA Conventional therapies can be effective in gATM carriers and should be considered before PARPi, which shows limited efficacy in this group. Men with gATM mutations warrant prioritization for novel treatment strategies.
Sections du résumé
BACKGROUND
Among men with metastatic prostate cancer, about 10% have germline alterations in DNA damage response genes. Most studies have examined BRCA2 alone or an aggregate of BRCA1/2 and ATM. Emerging data suggest that ATM mutations may have distinct biology and warrant individual evaluation. The objective of this study is to determine whether response to prostate cancer systemic therapies differs between men with germline mutations in ATM (gATM) and BRCA2 (gBRCA2).
METHODS
This is an international multicenter retrospective matched cohort study of men with prostate cancer harboring gATM or gBRCA2. PSA
RESULTS AND LIMITATIONS
The study included 45 gATM and 45 gBRCA2 patients, matched on stage and year of germline testing. Patients with gATM and gBRCA2 had similar age, Gleason grade, and PSA at diagnosis. We did not observe differences in PSA
CONCLUSIONS
Conventional therapies can be effective in gATM carriers and should be considered before PARPi, which shows limited efficacy in this group. Men with gATM mutations warrant prioritization for novel treatment strategies.
Identifiants
pubmed: 34516663
doi: 10.1002/pros.24236
pmc: PMC8563438
mid: NIHMS1738743
doi:
Substances chimiques
Androstenes
0
Antineoplastic Agents
0
BRCA2 Protein
0
BRCA2 protein, human
0
Benzamides
0
Nitriles
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Docetaxel
15H5577CQD
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Prostate-Specific Antigen
EC 3.4.21.77
abiraterone
G819A456D0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1382-1389Subventions
Organisme : NCI NIH HHS
ID : R50 CA221836
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097186
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009515
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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