HRD test results used in published and ongoing clinical trials for PARP inhibitor-treatment of ovarian cancer are not equivalent, according to the results of a study presented at the American Society of Clinical Oncology (ASCO) Annual Meeting (May 29-31, 2020).
While previous clinical trials have examined the utility of genomic instability test scores or gene panels to assess HRD for PARP inhibitor use in ovarian cancer, these methods may not be equivalent in accuracy.
Kirsten M Timms, Myriad Genetic Laboratories, Inc (Salt Lake City, UT), and colleagues designed an analysis to determine whether genomic instability scores and HRD testing produce comparable results in predicting PARP inhibitor response for patients with ovarian cancer. Researchers compared the proportion of patients identified as candidates for PARP inhibitor use by two measures of HRD (percentage loss of heterozygosity and 11-gene panel) with the myChoice HRD test – and FDA-approved HRD test that includes BRCA1/2 mutation status and three measures of genomic instability.
A whole-genome SNP analysis was used to reconstruct ovarian tumor genomic profiles in order to calculate myChoice HRD scores and percentage loss of heterozygosity in two cohorts – a clinical laboratory cohort (n = 3278) and patients from the SCOTROC4 clinical trial (n = 248). Screening for an 11-gene panel was performed for a subset of tumors from the SCOTROC4 trial (n = 187).
Researchers noted that patient samples were considered positive if the myChoice HRD score was above the threshold (scores of 42 and 33 were assessed), percentage loss of heterozygosity was above a 16% threshold, or a pathogenic variant was found in one of the 11 HR genes.
Correlation between positive results from percentage loss of heterozygosity and the 11-gene panel were compared with results from myChoice HRD testing. Percent of positive agreement was determined as the proportion of positive test results from myChoice that were also positive by percentage loss of heterozygosity or the 11-gene panel.
Results of the comparison showed that 19% to 61% of patients identified as positive by the myChoice HRD test would have been missed by percentage loss of heterozygosity or the 11-gene panel in the clinical testing cohort and the SCOTROC4 cohort. This finding led authors of the study to conclude that HRD test results used in published and ongoing clinical trials are not equivalent and should not be considered interchangeable in predicting PARP inhibitor response in patients with ovarian cancer in clinical practice.—Zachary Bessette
