The diagnostic landscape of HRD testing based on cross-sectional survey of physicians and molecular biologists conducting testing (INDICATOR ONE).
Authors: Coleman Robert L. , Hada Manila , French Tim , Ozgoren Ozan , John Ellie , Stirnadel-Farrant Heide , Schweikert Bernd , Clark Dayna R. , Leary Alexandra 
Published: June 2023

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Background: Homologous recombination deficiency (HRD) occurs in approximately 50% of epithelial ovarian cancer (OC) cases. As HRD-positive tumors are more sensitive to poly(ADP-ribose) polymerase inhibitors (PARPi), HRD testing (determined by BRCAm and genomic instability score) identifies advanced ovarian cancer (AOC) patients who will benefit most from PARPi treatment . The value of these tests is recognized by guidelines to inform PARPi maintenance treatment decisions following first-line chemotherapy. This study characterizes the current testing landscape. Methods: This non-interventional, cross-sectional, web-based survey will be repeated in three waves, 9-12 months apart. Reported results are from Survey Wave 1 open from July to November 2022 and conducted among physicians and clinical laboratory heads/molecular biologists in the US and Europe (UK, France, Germany, Austria). Participants were recruited from clinical sites/laboratories known to be conducting HRD testing and via a standing physician panel. Results: Responses were received from 287 eligible participants (representing invitees from ~9% sites and < 2% panelists), 265 of whom completed the full survey (Europe: 153, US: 112; 228 physicians, 37 clinical laboratory heads/molecular biologists). Physicians ordered HRD testing for 70% ± 27% (mean ± SD) of newly diagnosed AOC patients. Nearly all physicians ordered the test to inform treatment decisions (n = 222; 97%). Physicians were most likely to conduct testing at stage 3 or 4 of OC diagnosis (Europe: n = 89, 64%; US: n = 63, 71%), followed by OC diagnosis regardless of stage (Europe: n = 51, 37%, US: n = 51, 57%). When European participants selected all types of tests used MyChoice CDx, Myriad Genetics (n = 82, 54%) was most commonly selected, followed by FoundationOne CDx, Foundation Medicine (n = 38, 25%). US participants used FoundationOne CDx (n = 62, 55%), followed by MyChoice CDx (n = 49, 44%), and QIAGEN QIASeq HRD (n = 38, 34%). Test costs were often partially (Europe: n = 47; 27%; US: n = 125; 53%) or fully covered (Europe: n = 89; 51%; US: n = 48; 21%). Results were received within 10 ± 6 (mean ± SD) working days in the US and 16 ± 11 working days in Europe. Testing guided treatment decisions ‘always/often’ (Europe: n = 117, 84%; US: n = 65, 73%) or ‘sometimes’ (Europe: n = 21, 15%; US: n = 23, 26%). Most European (n = 108, 78%) and US (n = 71, 80%) institutions offered genetic counselling. Conclusions: Among physicians and molecular biologists known to be conducting HRD testing, most newly diagnosed AOC patients were tested for HRD, and results usually played a role in treatment decisions. Variations in testing between the US and Europe include test types, test cost coverage, and time to receive results. Differences indicate potential areas for improvement in HRD testing to further benefit patients.