Real-world validation study with over 500 tumor samples shows MyChoice CDx Plus can be performed in a decentralized setting¹

1^st December 2022 Myriad Genetics’ MyChoice CDx Plus Diagnostic Test is validated for decentralized evaluation of Homologous Recombination Deficiency (HRD) by assessing genomic instability status (GIS) and tumor BRCA 1/2 mutations in academic local molecular pathology laboratories, according to a newly published, real-world validation study.

Published in the December issue of the Journal of Molecular Diagnostics,¹ the study led by Denkert et al. was titled, ‘Homologous Recombination Deficiency as an ovarian cancer biomarker in a Real-World cohort validation of decentralized genomic profiling’. The results support introduction of the MyChoice assay in academic local molecular pathology laboratories, meaning wider access to precision medicine for patients with ovarian cancer worldwide.

“Validated HRD testing should be offered to all patients with high-grade ovarian cancer,” said Sylvette Delee, M.D., Director of International Medical Affairs, Myriad Genetics. “High concordance of the Myriad GIS in a local laboratory is an important milestone for Myriad to optimize access for both patients and physicians to the gold standard assay. Results show that a standardized central laboratory test can safely be transferred to an academic molecular pathology laboratory with highly consistent results.”.

The Denkert et al. study compared HRD status from 514 ovarian cancer samples referred to two labs:

• The molecular pathology laboratory of the Philipps-Universität Marburg (UMR) in Germany
• The central diagnostic laboratory of Myriad Genetics in Salt Lake City, USA

End points included concordance of homologous recombination deficiency (HRD) status and difference in GIS between the two labs.

GIS is a novel and proprietary measurement used by MyChoice CDx Plus which evaluates three key molecular biomarkers; large-scale state transitions (LSTs), telomeric allelic imbalance (TAI), and loss of heterozygosity (LOH).

MyChoice is the only clinically validated and US Food and Drug Administration-approved, PMDA and CE marked molecular HRD test in ovarian cancer. The European Medicines Agency states that genomic instability status should be determined by an experienced laboratory using a validated test including LSTs, TAI, and LOH.

Results showed the percentage of HRD positive tumors in this real-life cohort (38.9%) was similar to the proportion observed in the recently published PAOLA-1 trial,² with a high concordance between the central and local lab. Researchers observed a 96.9% GIS-status concordance (p < 0.000001) and 97.1% HRD-status concordance between the two labs.

The growing landscape of effective new therapy combinations for HRD positive high-grade serous ovarian cancers with PARPi (such as bevacizumab and olaparib combination²), has created a need for HRD assays that can be accurately performed in a decentralized setting. These real-world validation results in the MyChoice CDx Plus HRD test provide the first evidence that this need can be fulfilled, and support the introduction of the MyChoice HRD assay in academic local molecular pathology labs.

“The successful decentralized validation of the Myriad HRD assay opens up new opportunities for HRD testing, because it allows academic centres to use the validated clinical trial assay with full control of diagnostic procedures and to perform in-house validations and quality checks,” said Professor Carsten Denkert, Institute of Pathology, Philipps Universität Marburg. “This validation shows that the Myriad HRD assay is a method that can be implemented in other academic research laboratories.”

Download the clinical summary of the study here.

To get further information on the assay, please send a message to info@myriadgenetics.eu

About the study

The ‘Homologous Recombination Deficiency as an ovarian cancer biomarker in a Real-World cohort validation of decentralized genomic profiling’ study evaluated 514 ovarian cancer samples referred to the molecular pathology laboratory of Philipps-Universität Marburg (UMR) in Germany. Samples were referred to UMR between November 2020 and July 2021 and assessed in parallel by Myriad Genetics’ central diagnostic laboratory in Salt Lake City, USA.

Patients’ tumor characteristics showed 89% being high-grade serous ovarian cancers (HGSOC). Non-HGSOC cancers were also included in the analysis. HRD was assessed by next-generation sequencing, using the standardized MyChoice HRD assay, with a predefined cut-off point of 42 for a positive genomic instability score (GIS).

End points included concordance of HRD status and GIS between the two laboratories.

Download the clinical summary here.

About Myriad Genetics

Myriad Genetics is a leading genetic testing and precision medicine company dedicated to advancing health and well-being for all. Myriad develops and offers genetic tests that help assess the risk of developing disease or disease progression and guide treatment decisions across medical specialties where genetic insights can significantly improve patient care and lower healthcare costs. Fast Company named Myriad among the World’s Most Innovative Companies for 2022. For more information, visit https://myriadgenetics.eu/.

Myriad, the Myriad logo, MyChoice and the MyChoice logo, are trademarks or registered trademarks of Myriad Genetics, Inc. © 2023 Myriad Genetics, Inc. All rights reserved.

References

1. Denkert, Carsten, et al. “Homologous Recombination Deficiency as an Ovarian Cancer Biomarker in a Real-World Cohort.” The Journal of Molecular Diagnostics, vol. 24, no. 12, 2022, pp. 1254-1263.
2. Ray-Coquard, Isabelle et al. “Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer.” New England Journal of Medicine, vol. 381, no. 25, 2019, pp. 2416-2428.