Novel Genomic Instability Scar Test for Detecting Homologous Repair Deficiency, Predicting Olaparib Sensitivity Among Patients With Ovarian Cancer
The academic-developed genomic instability score test, Genomic Instability Scar (GIScar), found to reliably detect homologous repair deficiency (HRD), as well as sensitivity to olaparib among patients with ovarian cancer, according to a recent study.
Raphaël Leman, MD, Centre François Baclesse, Caen, France, and coauthors wrote “in many countries, access to HRD testing is problematic and the failure rate is high,” which poses a problem for optimal treatment with maintenance PARP inhibition for patients with ovarian cancer.
Dr Leman and coauthors developed the GIScar tool via targeted sequencing of a 127-gene panel to determine HRD status. GIScar was trained on noninterventional studies including 250 prospectively collected ovarian tumor samples and validated using 469 DNA tumor samples collected in the PALOMA-1 trial. The predictive value was compared to Myriad Genetics MyChoice (MGMC).
Among the samples from the PALOMA-1 trial, GIScar identified more HRD-positive tumors than MGMC and had a lower proportion of inconclusive results (1% vs 9%, respectively). Tumors that had been identified as HRD positive by GIScar but HRD negative by MGMC (n = 16) had better PFS with olaparib (hazard ratio [HR], 0.23). The HR for progression-free survival with olaparib compared with placebo was 0.45 in BRCA-mutated tumors identified as HRD-positive by GIScar, 0.50 in BRCA-wild-type HRD positive tumors, and 1.02 in HRD-negative tumors.
Dr Leman et al, concluded “GIScar is a valuable diagnostic tool, reliably detected HRD and predicting sensitivity to olaparib for ovarian cancer.” They added, “GIScar is easily implemented into diagnostic laboratories with a rapid turnaround.”
Source:
Leman R, Muller E, Legros A, et al. Validation of the clinical use of GIScar, an academic-developed genomic instability score predicting sensitivity to maintenance olaparib for ovarian cancer. Clin Cancer Res. Published online September 26, 2023. doi:10.1158/1078-0432.CCR-23-0898
