Technical evaluation of commercially available homologous recombination deficiency assays using MyChoice CDx as...

Identifying tumors with homologous recombination deficiency (HRD) is critical to determining appropriate treatment options for advanced ovarian cancer. We investigated concordance of HRD status and other associated biomarkers between Food and Drug Administration-approved MyChoice® CDx and 4 assays commercially available in various regions.

DNA was isolated from pretreatment tissue samples from trial participants with platinum-sensitive relapsed ovarian cancer without a germline BRCA mutation (BRCAm). HRD status was assessed using MyChoice CDx and FoundationOne®CDx, SOPHiA DDM™ Dx HRD Solution, Thermo Fisher Oncomine™ Comprehensive Assay Plus (OCA Plus), and whole-genome copy number variation-based Thermo Fisher OncoScan™. Therapeutic efficacy was simulated in silico using data from the phase 3 PAOLA-1 study.

Biomarker assessment success rate was ≥87% for all next-generation sequencing-based assays and 71.6% for Thermo Fisher OncoScan. With MyChoice CDx as reference, for HRD status, overall percentage agreement (OPA) ranged 76.0%-88.7%; positive percentage agreement (PPA) ranged 81.6%-93.8%, and negative percentage agreement (NPA) ranged 70.3%-90.4%. For genomic instability, OPA ranged 74.7%-87.5%, PPA ranged 67.6%-91.5%, and NPA ranged 71.1%-88.4%. For BRCAm status, OPA ranged 90.0%-96.9%, PPA ranged 50.0%-86.4%, and NPA ranged 94.4%-100%. Among simulated HRD-positive participants, mean progression-free survival hazard ratio was 0.40 at PPA of 80% and NPA of 85%, and 0.38 at PPA of 75% and NPA of 90%.

Using MyChoice CDx as reference, commercially available assays showed concordance in detecting HRD, genomic instability, and BRCA mutations, indicating their potential clinical utility in identifying appropriate treatment options for ovarian cancer.