Role of Poly (ADP-Ribose) Polymerase inhibitors beyond BReast CAncer Gene-mutated ovarian tumours: definition of homologous recombination deficiency?
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Clinical Trials as Topic
Female
Humans
Maintenance Chemotherapy
Mutation
Ovarian Neoplasms
/ drug therapy
Poly(ADP-ribose) Polymerase Inhibitors
/ administration & dosage
Randomized Controlled Trials as Topic
Recombinational DNA Repair
Journal
Current opinion in oncology
ISSN: 1531-703X
Titre abrégé: Curr Opin Oncol
Pays: United States
ID NLM: 9007265
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
entrez:
16
8
2020
pubmed:
17
8
2020
medline:
23
12
2020
Statut:
ppublish
Résumé
PARP inhibitors have transformed the management of BRCA mutant (BRCA) high-grade serous and endometroid ovarian cancer (HGOC). However, it is clear that the benefit can be extended beyond this subgroup, particularly to those cancers with homologous recombination repair deficiency (HRD). We review emerging molecular and clinical data to support the use of PARP inhibitors in HRD HGOC and discuss the advantages and disadvantages of different HRD assays. Several phase 3 trials support the use of PARP inhibitor maintenance therapy beyond those patients with BRCA in the first-line and platinum-sensitive relapse setting. Many of these studies included HRD testing and it is clear, regardless of the assay used, that an incremental reduction in benefit is observed from BRCA tumours to HRD to homologous recombination proficient tumours. However, although currently available HRD assays predict the magnitude of benefit from PARP inhibitors, they consistently fail to identify a subgroup of patients who do not benefit. Clinical data support the use of PARP inhibitor maintenance therapy beyond BRCA patients. Current HRD tests lack negative predictive value and more research is required to develop a composite HRD assay that provides a dynamic readout of HRD status.
Identifiants
pubmed: 32796232
doi: 10.1097/CCO.0000000000000660
pii: 00001622-202009000-00008
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
442-450Subventions
Organisme : Chief Scientist Office
ID : SCD/11
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
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