Abstract 758P
Background
In the last years, Poly(ADP-ribose)-polymerase 1 inhibitors (PARPi) became a standard treatment option for patients with recurrent platinum-sensitive ovarian cancer and recently have been approved for maintenance use in the first-line setting. Biomarker subgroup analysis consistently revealed higher benefit for patients with homologous recombination deficiency (HRD; BRCA1/2m and/or genomic instability (GIS) positive), demonstrating the value of biomarker testing in this setting. The Myriad MyChoice assay has been the most commonly used HRD assay applied in the majority of clinical studies. However, several other assays can also be applied to determine HRD, which may have potential for clinical use. Here, we compare the performance of some of these alternative HRD assays with Myriad MyChoice.
Methods
DNA from high-grade ovarian cancer was extracted from formalin-fixed paraffin embedded tissue blocks of cases with known Myriad MyChoice scores. HRD status was measured by several molecular assays (CytoSNP, AmoyDX, Oncoscan) applying different bioinformatics algorithms. HRD datasets were compared and correlated to BRCA1/2 mutational data.
Results
Initial results demonstrate that HRD scores show high concordances between the assays investigated, including Myriad MyChoice (Pearson correlation, r>0.8 for all comparisons). When the prespecified cutoff of 42 was applied, between 46% and 54% of the cases were positive, according to k-statistics a substantial concordance between assays was seen (k>0.75 for all comparisons). Between 27% and 39% of the HRD positive cases were BRCA wildtype. Single discordant cases usually had suboptimal DNA quantity/quality.
Conclusions
Assays for HRD assessment show a substantial concordance, both in between each other but also in correlation to the current standard assay, Myriad MyChoice. The study will be continued until 100 cases are included.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AstraZeneca.
Disclosure
W. Weichert: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AtraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Boehringer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Ilumina; Financial Interests, Personal, Advisory Board: Agilent; Financial Interests, Personal, Advisory Board: ADC; Financial Interests, Personal, Advisory Board: Molecular Health; Financial Interests, Personal, Advisory Board: Glaxo Smith Kline; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: AstraZeneca. E.I. Braicu: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Molecular Health; Financial Interests, Institutional, Research Grant: Roche Diagnostics; Financial Interests, Personal, Advisory Board: Abbvie; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board, Honoraria/Expenses: AstraZeneca; Financial Interests, Personal, Advisory Board, Honoraria/Expenses: Clovis; Financial Interests, Personal, Advisory Board, Honoraria/Expenses: MSD; Financial Interests, Personal, Advisory Board, Honoraria/Expenses: GSK; Financial Interests, Personal, Advisory Board, Honoraria/Expenses: Roche; Financial Interests, Personal, Advisory Board, Honoraria/Expenses: Tesaro; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Molecular Health. M.C. Demes: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Diaceutics; Financial Interests, Personal, Invited Speaker: Biocartis; Financial Interests, Personal, Invited Speaker: Sophia Genetics. V. Endris: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Thermo Fisher. L. Heukamp: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Agilent. M. Hummel: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Pierre Fabre. U. Lehmann: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Thermo Fisher; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Other, Congress expenditures: BMS. S. Merkelbach-Bruse: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Targos; Financial Interests, Personal, Advisory Board: Molecular Health; Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: BMS; Non-Financial Interests, Personal, Advisory Role: Janssen. N. Pfarr: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Ilumina; Financial Interests, Personal, Invited Speaker: Thermo Fisher Scientific. J. Sehouli: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Clovis; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Royalties: Tesaro; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Vifor Pharma; Financial Interests, Personal, Invited Speaker: Hexal AG; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Merck/Pfizer; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche ; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Novocure; Financial Interests, Personal, Advisory Role: Oncoinvent. J. Siemanowski: Financial Interests, Personal, Advisory Board: MDK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Biocartis. A. Stenzinger: Financial Interests, Personal, Advisory Board: AIGnostics; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Thermo Fisher; Financial Interests, Personal, Advisory Board: Ilumina; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Incyte. P. Wild: Financial Interests, Personal, Invited Speaker, consulting fees: Bayer; Financial Interests, Personal, Invited Speaker, consulting fees: Janssen; Financial Interests, Personal, Invited Speaker, consulting fees: Novartis; Financial Interests, Personal, Invited Speaker, consulting fees: Roche; Financial Interests, Personal, Invited Speaker, consulting fees: MSD; Financial Interests, Personal, Invited Speaker, consulting fees: Astellas Pharma; Financial Interests, Personal, Invited Speaker, consulting fees: BMS; Financial Interests, Personal, Invited Speaker, consulting fees: Thermo Fisher Scientific; Financial Interests, Personal, Invited Speaker, consulting fees: Molecular Health; Financial Interests, Personal, Invited Speaker, consulting fees: Sophia Genetics; Financial Interests, Personal, Invited Speaker, consulting fees: Qiagen; Financial Interests, Personal, Invited Speaker, consulting fees: Lilly; Financial Interests, Personal, Invited Speaker, consulting fees: AstraZeneca. All other authors have declared no conflicts of interest.