UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Role of Poly (ADP-Ribose) Polymerase inhibitors beyond BReast CAncer Gene-mutated ovarian tumours: definition of homologous recombination deficiency?

Gourley, C; Miller, RE; Hollis, RL; Ledermann, JA; (2020) Role of Poly (ADP-Ribose) Polymerase inhibitors beyond BReast CAncer Gene-mutated ovarian tumours: definition of homologous recombination deficiency? Current Opinion in Oncology , 32 (5) pp. 442-450. 10.1097/CCO.0000000000000660. Green open access

[thumbnail of COON-S-20-00032-_submitted.pdf]
Preview
Text
COON-S-20-00032-_submitted.pdf - Accepted Version

Download (1MB) | Preview

Abstract

Purpose of review: PARP inhibitors have transformed the management of BRCA mutant (BRCAmut) 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. Recent findings: Several phase 3 trials support the use of PARP inhibitor maintenance therapy beyond those patients with BRCAmut 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 BRCAmut 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. Summary: Clinical data support the use of PARP inhibitor maintenance therapy beyond BRCAmut 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.

Type: Article
Title: Role of Poly (ADP-Ribose) Polymerase inhibitors beyond BReast CAncer Gene-mutated ovarian tumours: definition of homologous recombination deficiency?
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/CCO.0000000000000660
Publisher version: https://doi.org/10.1097/CCO.0000000000000660
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Ovarian cancer, PARP inhibitors, BRCA, homologous recombination deficiency (HRD)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
URI: https://discovery.ucl.ac.uk/id/eprint/10109790
Downloads since deposit
112Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item