Abstract 575P
Background
Maintenance therapy with a poly(ADP-ribose) polymerase-1/2 inhibitor (PARPi) improves survival outcomes in women with high-grade serous or endometroid ovarian cancer (HGS/EOC) whose disease responds to platinum-taxane chemotherapy, with the greatest benefit reported in BRCA-mutant/Homologous Recombination Deficient (HRD)-tumours. We report the prevalence of BRCA-mutant/HRD-tumours in women with newly diagnosed FIGO stage III/IV HGS/EOC in England, Wales and Northern Ireland between April 2021 and April 2022. These data represent the first year that routine HRD testing was available through the NHS.
Methods
Eligibility criteria included newly diagnosed FIGO stage III/IV HGS/EOC. The Myriad myChoice® HRD assay was used to detect pathogenic BRCA1/2 variants and a genomic instability score (GIS) in formalin-fixed paraffin-embedded tumour tissue. Testing was performed during standard-of-care first-line therapy pathways. All patients gave informed consent for tumour testing. No cases were included that were tested as part of a clinical trial. Testing was co-ordinated by the NHS Genomic Hub Laboratory network.
Results
Tumour BRCA1/2 and GIS testing was requested for 2,829 patients. 2,474 (87.5%) and 2,178 (77.0%) patients were successfully tested for BRCA1/2 or GIS, respectively. 385 (15.6%) BRCA1/2 pathogenic variants were detected (BRCA1=220; BRCA2=165). The GIS was ≥42 in 814 (37.4%) patients. 510 (23.4%) patients had tumour BRCA1/2 wild-type and a GIS ≥42. GIS had a bimodal distribution, with BRCA1/2-mutant tumours having higher scores than wild-type tumours.
Conclusions
In this study of women with newly diagnosed FIGO stage III/IV HGS/EOC, 895 (36.2%) were found to have a BRCA1/2 mutation and/or a GIS ≥42, and therefore had the opportunity to benefit from first-line PARPi maintenance therapy. This is the largest real-world evidence cohort for the prevalence of HRD-tumours in HGS/EOC. These data highlight the importance of HRD testing to optimise outcomes for eligible women. The rapid uptake of HRD testing in England, Wales and Northern Ireland also demonstrates the power of centralised NHS funding, centre specialisation and the Genomic Hub Laboratory network.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Sundar: Financial Interests, Personal, Invited Speaker, invited speaker for conference: AstraZeneca, MSD; Financial Interests, Personal, Invited Speaker, invited speaker at workshop: GSK; Non-Financial Interests, Leadership Role, President of the British Gynaecological Cancer Society: BGCS. S. Nicum: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis; Financial Interests, Personal, Stocks/Shares: GSK; Financial Interests, Institutional, Funding: AstraZeneca. J.D. Brenton: Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Tailor Bio; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Tailor Bio; Financial Interests, Institutional, Invited Speaker: Clovis Oncology, Aprea AB; Non-Financial Interests, Member: Association of Cancer Physicians. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna; Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro; Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): Astrazeneca; Non-Financial Interests, Advisory Role: Epsilogen; Non-Financial Interests, Other, Member of membership committee: ESGO; Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated): Lady GardenFoundation Charity. I. McNeish: Financial Interests, Personal, Advisory Board, Advisory Boards: Clovis Oncology; Financial Interests, Personal, Advisory Board, Advisory Boards and travel: AstraZeneca, GSK; Financial Interests, Personal, Advisory Board: Roche, Alkermes, OncoC4, Theolytics; Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Invited Speaker, Trustee of this charity: Worldwide Cancer Research. J.A. Ledermann: Financial Interests, Personal, Advisory Board, Advisory Board and Speaker Fees: AstraZeneca, Clovis Oncology, GSK; Financial Interests, Personal, Advisory Board: Artios Pharma, Eisai, Merck/MSD, Pfizer, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Ellipses; Financial Interests, Personal, Other, Independent Data Monitoring Committee: Regeneron; Financial Interests, Institutional, Research Grant, Clinical Research University: AstraZeneca, MSD/Merck; Financial Interests, Institutional, Other, Clinical Trials- hospital: Clovis Oncology, Pfizer, Merck/MSD, Eisai, AstraZeneca, GSK; Non-Financial Interests, Leadership Role, Vice President ( 2019-2021): European Society of Gynaecological Oncology; Other, Other, Associate Editor: Therapeutic Advances in Medical Oncology: Sage Publishing. All other authors have declared no conflicts of interest.