Introduction/Background*Homologous recombination deficiency (HRD), resulting from defects in the homologous recombination repair pathway, is a common feature of high-grade serous (HGS) ovarian cancer (OC) and predictive of sensitivity to PARP inhibitors. Developing reliable methods to determine HRD status of tumours is important to optimise clinical benefits of PARP inhibitors. Evaluation of HRD by genomic instability or BRCA1 and/or BRCA2 mutation (BRCAm) is emerging as an important tool in OC. Here, we present a performance evaluation of two available molecular assays with potential to identify HRD-positive tumours by genomic instability in OC, compared with Myriad myChoice CDx (Myriad Genetic Laboratories, Inc.; US FDA-approved and EU CE-IVD marked).
Methodology Analytical performance of FoundationOne CDx (F1CDx; Foundation Medicine, Inc.), a US FDA-approved complementary diagnostic for genomic loss of heterozygosity in OC, and AmoyDx HRD Focus Panel (Amoy Diagnostics Co., Ltd) assays (both EU CE-IVD marked) were evaluated in a commercial clinical laboratory setting. Assay performance was evaluated as positive (PPA), negative (NPA) and overall (OPA) percent agreement with HRD status (determined by myChoice CDx) of archival samples from patients with non-gBRCAm platinum-sensitive HGS or endometrioid OC tumours. The assays determine genomic instability by different methodologies. Data are summarised descriptively.
Result(s)*Both F1CDx and AmoyDx HRD Focus Panel molecular HRD assays demonstrated analytical concordance with myChoice CDx, with differing levels of sensitivity and specificity at manufacturer-recommended cut-offs. F1CDx demonstrated the following agreements on genomic instability with myChoice CDx: PPA 67.6%, NPA 85.7% and OPA 77.0% (N=148). AmoyDx HRD Focus Panel demonstrated the following agreements on genomic instability with myChoice CDx: PPA 92.0%, NPA 52.1% and OPA 72.4% using the existing algorithm and PPA 88.0%, NPA 75.0% and OPA 81.6% using a newly developed algorithm (N=98). Assay concordance for BRCAm detection was not undertaken because of limited BRCAm tumour samples.
Conclusion*F1CDx and AmoyDx HRD Focus Panel molecular HRD assays demonstrated concordance with, but not full equivalence to, myChoice CDx. Having multiple assays (providing their performance is adequate) to identify patients whose tumours harbour HRD is important to inform treatment decisions, as well as providing greater choice for clinicians and clinical laboratories.
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