Evaluation of the 1021-HRD assay compared to established HRD testing platforms in ovarian cancer.

PARP inhibitors have revolutionized ovarian cancer treatment, with benefits strongly linked to the presence of Homologous Recombination Deficiency (HRD). Although HRD testing was originally conducted on centralized platforms, there is growing demand for scalable, accessible, and robust solutions capable of supporting expanded clinical utilization. In the present study, a decentralized NGS-based assay was compared for its ability to effectively identify HRD positive patients when compared to the reference assay as well as other testing platforms. Eighty-two cases of ovarian cancer patients previously tested using the reference HRD assay (Myriad MyChoice® CDx assay) were evaluated by an NGS based HRD assay, the 1021-HRD assay (GenePlus), that provides genomic instability (GI) analysis along with tumor molecular profiling. HRD status, GI status (referred to as HRD-score), and even BRCA1/2 mutation detection were assessed for concordance with the reference test and the analytical accuracy of the assay was calculated. Additionally, GI alignment across alternative HRD testing platforms was examined. Finally, the association between key tumor alterations and the HRD status was evaluated. The 1021-HRD assay demonstrated an overall HRD classification agreement of approximately 92.68 % (κ = 0.841) in comparison to the reference method, as evidenced by the results, with 81.25 % specificity and 100 % sensitivity. These features generally suggest consistent performance, with only minor discrepancies observed. The BRCA1/2 alterations detected were 97.56 % in agreement with the approved assay. The Pearson r value of 0.878 indicates a strong correlation between the GI values obtained. The assay's capacity to detect non-BRCA1/2 HRD phenotypes was verified by the observation that 55.56 % of BRCA-wildtype malignancies were HRD-positive. Of particular interest, combining molecular profiling with GI analysis, the assay identified additional actionable alterations in 65 % of the cases, revealing clinically relevant biomarkers beyond the homologous recombination pathway. This wide-ranging approach may provide more diagnostic and therapeutic insight than HRD testing alone. In conclusion, the 1021-HRD assay is a dependable, decentralized alternative for HRD testing. It can provide a more comprehensive genomic characterization and exhibits remarkable analytical concordance with current standards. Its combined format and accessibility render it well-suited for real-world use in personalized ovarian cancer care. Its additional capacity to reveal more extensive tumor genomic alterations improves clinical decision-making and underscores the importance of integrating HRD scoring with comprehensive molecular profiling in personalized oncology.