Introduction

At SeqOne, we develop state-of-the-art genomics analysis tools for clinical applications in oncology and rare disease. Over the past eight months, we have had the opportunity to collaborate with the North West Genomic Laboratory Hub (North West GLH) who are now using our HRD test in clinical service. This case study highlights their journey to implement an in-house HRD test that is a cost-effective and accurate solution for predicting ovarian cancer patients’ responses to PARP inhibitors.

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The Challenge

Ovarian cancer presents a significant challenge for molecular diagnostic labs, with about 45% of cases exhibiting Homologous Recombination Deficiency (HRD). Identifying HRD is crucial for assessing treatment options and guiding personalized treatment strategies. Historically the Myriad myChoice™ platform solution had been used and has been the gold standard  validated through the PAOLA-1 clinical trial. However, North West GLH sought a more cost-effective and equally reliable alternative, which they could implement locally.

THE SOLUTION: SEQONE'S HRD PLATFORM

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Why North West GLH Chose SeqOne

  1. ‍Compatibility: SeqOne’s HRD solution seamlessly integrated with North West GLH’s existing workflows for solid tumor panel testing
  2. ‍Validation on Clinical Samples: North West GLH validated SeqOne’s HRD platform solution using formalin-fixed, paraffin-embedded (FFPE) tumor specimens, with results compared to Myriad myChoice™.‍
  3. High concordance with Myriad myChoice™ test: SeqOne’s HRD platform solution demonstrates 96% agreement in HRD status as Myriad myChoice™ test across the 28 tested samples.

Validation Process

  • Clinical Sample Testing: A total of 28 samples were analyzed with both SeqOne’s HRD platform solution and the Myriad myChoice™ test.
  • High Concordance: The SomaHRD v1.2 platform solution exhibited a high concordance with only one sample showing a discrepancy compared to the Myriad myChoice™ test.
  • Clinical Trial Data: Analysis of samples from the PAOLA-1 trial, performed by SeqOne confirmed that SeqOne’s HRD platform solution is comparable to the Myriad myChoice™ test in predicting responses to Olaparib.

Implementation and Results

In December 2023, North West GLH launched the new genomic instability testing service using SeqOne’s HRD platform solution.

Detailed Data and Results

  • Sample Size and Diversity: The validation included 28 clinical samples from patients with serous ovarian carcinoma. DNA concentrations ranged from 1-143 ng/µl, ensuring robustness across different sample qualities.
  • Comparative Performance in the PAOLA-1 cohort: SeqOne’s HRD platform solution v1.2 achieved a sensitivity of 98% and specificity of 95%, compared to the Myriad myChoice™ test.
  • Comparative performance in the NorthWest GLH validation cohort: Considering that the Myriad myChoice™ test provides the baseline result for the 28 clinical samples, only one sample showed a discrepancy, showcasing reliability of SeqOne’s HRD v1.2 platform solution.  
  • Clinical Outcomes in the PAOLA-1 cohort: In patients with HRD-positive tumors treated with olaparib plus bevacizumab, the PFS Hazard Ratio (HR) was 0.38 (95% CI; 0.26–0.54) with SeqOne assay and 0.32 (95% CI; 0.22–0.45) with the Myriad assay (Figure 1).
  • Similar overall statistics in the routine of NorthWest GLH: Routine testing currently shows similar ratios of patients tested with the SeqOne HRD platform, resulting in 30% positive, 55% negative and approximately 10% inconclusive rate compared to the previously used Myriad myChoice™ test (Figure 2).
Figure 1: SeqOne accurately predicts survival in genomic instability positive patients in the PAOLA-1 trial similar to the Myriad myChoiceTM test.
Figure 2: New in-house workflow reduces turnaround time from 22 days to 21 days, with fewer delayed reports compared to Myriad.

Workflow Efficiency

By choosing SeqOne, North West GLH achieved:

  • Greater Control: In-house testing allowed more control over workflows and turnaround times.
  • Quicker Turnaround: Average reporting times were reduced to 20 days, with only 21% of referrals reported after 21 days compared to 44% with Myriad myChoice™ (Figure 3).
  • Flexibility: SeqOne’s whitebox approach allowed North West GLH to feel confident and educated about the test they implemented in house.
Figure 3: New lab workflow enhances efficiency, with critical QC steps ensuring high-quality genomic instability testing in-house.

Conclusion

The collaboration between SeqOne and North West GLH highlights the efficacy and reliability of SeqOne’s HRD platform solution as a robust alternative to the Myriad myChoice™ test. This partnership underscores our commitment to advancing personalized medicine in oncology, providing accurate and cost-effective genomic testing solutions.

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“The big advantage of using SeqOne for us is how transparent the process is: we can get high-resolution information on each sample and understand in detail how the genomic instability score is calculated. This gives us additional confidence when reporting clinical results to the doctors and patients we serve.” - Joe Shaw, Clinical Scientist at North West GLH
About SeqOne

SeqOne is a leading European provider of AI-powered software for next-generation sequencing (NGS) data analysis in oncology and rare diseases. Its cloud-based platform transforms complex genomic data into fast, precise, and actionable insights, supporting molecular labs in delivering life-saving diagnoses and treatments. The SeqOne Platform is a CE-IVD Class C certified under IVDR in vitro diagnostic medical device. Driven by the vision of personalized medicine for every patient, everywhere, SeqOne is scaling the future of genomic medicine—one lab at a time.

For more information, visit seqone.com.

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References
  • Boidot R, Blum MGB, Wissler MP, et al. Clinical evaluation of a low-coverage whole-genome test for detecting homologous recombination deficiency in ovarian cancer. Eur J Cancer. 2024;202:113978. doi:10.1016/j.ejca.2024.113978

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