Abstract 572P
Background
Poly(ADP-ribose)-polymerase 1 inhibitors (PARPi) are currently in use in certain clinical settings for patients with ovarian cancer. Patients with homologous recombination repair deficiency (HRD) within their tumor which was defined as present if BRCA was mutated (BRCAm) and/or HRD-associated genomic instability (GIS) scores were high, revealed higher benefits, demonstrating the value of biomarker testing in this context. Currently the Myriad MyChoice assay is the most commonly used assay for HRD detection in clinical studies but other molecular assays can also be applied. Here, we compare the performance of multiple molecular assays in determining GIS in high grade ovarian cancer.
Methods
DNA from high-grade epithelial ovarian cancer was extracted from formalin-fixed paraffin embedded tissue of cases with known Myriad MyChoice GIS scores. GIS was measured by CytoSNP, AmoyDX, Illumina TSO 500+, Thermo Fisher OCA+, Oncoscan, Agilent NOGGO GIS v1, Qiagen QIASeq HRD Panel, low pass whole genome sequencing and determined using different bioinformatics algorithms. Most assays were run twice, independently in two labs to allow for interlaboratory comparisons. GIS datasets were compared and correlated to BRCA mutation status.
Results
Up to 70 cases were analyzed per assay (range 13-70, final goal: assessment of 100 samples per assay). The application of different assays to assess GIS revealed high concordance/correlations of the GIS scores generated by the different assays, the concordance/correlation of GIS scores generated by the alternative assays to myChoice generated GIS also ranged from very substantial to nearly perfect fit, depending on the assay and bioinformatics pipelines applied. Interlaboratory comparison of assays also showed high concordance of the GIS scores generated. As expected, high GIS scores were significantly associated with the presence of BRCA mutations for all assays.
Conclusions
Assays for GIS assessment show a concordance both between each other but also in correlation to the current standard assay, Myriad MyChoice. Interlaboratory variation was low. Our data suggest, that a variety of assays in principle could be used to asses GIS in the clinical setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AstraZeneca.
Disclosure
W. Weichert: Financial Interests, Institutional, Research Grant: Roche, BMS, AstraZeneca, MSD; Financial Interests, Personal, Advisory Board: Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, Janssen, Amgen, Astellas, Illumina, Eisai, Siemens, Agilent, GSK, ADC, Molecular Health. I. Braicu: Financial Interests, Institutional, Research Grant: Bayer, MSD, Roche, AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD, straZeneca, Clovis, Roche; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, Clovis, NOGGO; Financial Interests, Personal, Other, Travel: Covis, Roche. M. Demes: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Biocartis, Diaceutics, Roche, Sophia Genetics. L.C. Heukamp: Financial Interests, Personal, Advisory Role: Agilent, AstraZeneca, Boehringer, SmartinMedia, Pfizer, Amgen. M. Hummel: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, BMS, MSD, Lilly, Roche. U. Lehmann: Financial Interests, Personal, Invited Speaker, Writing: AstraZeneca; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Advisory Board: Novartis. S. Merkelbach-Bruse: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Roche, Novartis, GSK, MSD, Targos, Molecular Health, Merck, Oncowissen, Quip GmbH, Janssen, BMS. N. Pfarr: Financial Interests, Personal, Invited Speaker: Illumina, Novartis, Bayer, Roche, Roche, Astrazeneca, Thermo Fisher Scientific, Bristol Myers Squib; Financial Interests, Personal, Advisory Board: Novartis, Lilly; Financial Interests, Personal, Other, Traveling Support: Bristol Myers Squib; Non-Financial Interests, Institutional, Product Samples: Illumina, Thermo Fisher Scientific. R. Rad: Financial Interests, Institutional, Funding: Merck. J. Sehouli: Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Bayer, Clovis, GSK, Lilly, Tesaro; Financial Interests, Personal, Advisory Role: Tesaro, Merck, Pharma Mar, Clovis, AstraZeneca, Roche, GSK, MSD, Eisai, Novocure, Oncoinvent; Financial Interests, Personal, Invited Speaker: Tesaro, GSK, Pharma Mar, AstraZeneca, Clovis, Bayer, Roche, Vifor Pharma, Hexal, Novartis. J. Siemanowski: Financial Interests, Personal, Advisory Board: MDK; Financial Interests, Personal, Invited Speaker: Biocartis, Merck, Targos, AstraZeneca. A. Stenzinger: Financial Interests, Personal, Advisory Board: Aignostics, AstraZeneca, Janssen, Bayer, Seattle Genetics, Eli Lilly, Illumina, Thermo Fisher; Financial Interests, Institutional, Advisory Board: BMS, Takeda; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, MSD, Incyte; Financial Interests, Institutional, Research Grant: Bayer, Chugai, BMS, Incyte. C. Vollbrecht: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche. P.J. Wild: Financial Interests, Personal, Advisory Role: Bayer, Janssen, Novartis, Roche, MSD, Astellas, BMS, Thermo Fisher, Molecular Health, Guardant Health, Sophia Genetics, Qiagen, Lilly, Myriad, Hedera Dx, AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca. All other authors have declared no conflicts of interest.