Testing of newly diagnosed advanced high grade ovarian cancer (OC) patients with the Myriad Genetics MyChoice CDx Plus next generation sequencing-based in vitro diagnostic test emphasizes the need for public insurance coverage of genetic testing: Results of a national program by the Hellenic Society of Medical Oncology (HeSMO).

Abstract

e18520 Background: Homologous Recombination deficiency (HRD) represents a distinct entity in OC. Clinical data suggest that treatment selection can be based on both BRCA1/2 mutations and bearing Genomic Instability Status (GIS). Testing for GIS is critical in order to expand patients’ pool for targeted treatment. Myriad my Choice, is currently the only FDA approved test that can detect HRD by assessing BRCA1/BRCA2 mutation and GIS status in OC tumor specimens using 3 biomarkers: loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions. To address this need, HeSMO has initiated a national program to provide access to myChoice to newly diagnosed patients with high grade stage III/IV OC. Methods: Patients with newly diagnosed stage III/IV high grade OC were eligible to participate in this program. The specific performance characteristics of myChoice CDx assay were determined on FFPE tumor samples by the evaluation of a range of representative tumor BRCA1 and BRCA2 sequence variants (e.g. single nucleotide variants, insertions or deletions and variants in homopolymers), Large Rearrangements (e.g. deletions and duplications affecting single and multiple exons) and a representative range of GIS. The overall results are composed of two major components: GIS Status (positive or negative) and tumor (t) BRCA1/2 Status (positive or negative). The combined results form the basis of the overall interpretation of the myChoice CDx Myriad HRD Status. Results: From December 2020 to January 2022, 454 patients from all over the country were tested within this program. 220 patients (48.46%) had a positive GIS report and 179 (39.43%) had a negative one. Among GIS positive cases, 122 patients were tBRCAwt (26.87%) 78 patients were tBRCA mutated (17.18%) and 10 patients had suspected deleterious BRCA1/2 mutations (2.20%). Inconclusive was the report in 38 specimens (8.37%) and myChoice Lab failed to complete the analysis in 15 cases (3.30%). Furthermore, mutations were also detected in a number of other genes, including but not limited to, ATM, BRIP1, PALB2, RAD51C, RAD51D, FANCL, CHEK2. Conclusions: In our series, 48.46% of the patients with high grade OC tested as BRCA1/2 and/or GIS positive, in accordance with published data, underlying the clinical need to implement GIS testing in OC patients’ molecular evaluation. Apart from the significant implications for treatment possibilities in an expanded patients’ population, these results are important for cancer prevention. We strongly believe that our results will strengthen our efforts for reimbursement of such testing in high grade OC patients, and will serve as a roadmap for the establishment of local HRD testing solutions.