Objectives: The phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644) evaluated first-line standard therapy including bevacizumab in advanced ovarian cancer with the addition of maintenance olaparib or placebo. Significant improved progression-free survival (PFS) was observed in homologous recombination deficient (HRD) tumors, with or without BRCA mutation (BRCAm), tested with Myriad myChoice PLUS (Myriad test) in contradiction to homologous recombination proficient (HRP) tumors, revealing the need for HRD testing in first line. As part of the ENGOT European HRD initiative, we developed the 'Leuven' HRD test. To the best of our knowledge, this is the first presentation of an alternative academic laboratory-developed HRD test compared with the Myriad test including an analysis of the predictive value for olaparib efficacy (PFS) in first-line ovarian cancer. Methods: The Leuven HRD test was first developed on ovarian cancer tumor samples of the biobank of the University Hospitals Leuven. Then, we analyzed formalin-fixed paraffin-embedded (FFPE) derived DNA from 468 available ovarian cancer samples of the PAOLA-1/ENGOT-ov25 trial. We performed capture-based targeted resequencing of ±90,000 genome-wide single nucleotide polymorphisms (SNPs) at ±40x coverage, and coding exons of BRCA1, BRCA2, RAD51C, RAD51D, PALB2, BLM, BARD1, BRIP1 and TP53 at ±400x coverage. All samples were analyzed using the Leuven HRD and the Myriad test. The BRCAm status, genomic instability score (GIS) and HRD status (comprising both the BRCAm and GIS status) were compared between both tests. The main objective was to compare the predictive value of both tests for predicting PFS in the olaparib versus placebo arm. The Hazard Ratio (HR) and associated 95% confidence interval (CI) were calculated with the use of a Cox proportional hazards model. Results: Within a group of 468 patients with available tumor DNA samples, 317 (68%) and 151 (32%) patients were treated with olaparib and placebo, respectively. All samples were tested by the Myriad test first within the scope of the PAOLA-1 trial; remaining extracted DNA was used for the Leuven HRD testing. Positive percent agreement for the Leuven vs Myriad HRD status was 94%, negative percent agreement was 86% and the overall percent agreement was 91%. Prevalence of pathogenic BRCA variants was 147 (31%) with the Leuven HRR gene panel versus 151 (32%) with Myriad test. Tumors with a pathogenic BRCAm and/or GIS 56 were considered Leuven HRD positive (Myriad cutoff GIS 42). With the Leuven and Myriad test, patients were considered as HRD positive in 54% (n=254) and 52% (n=242), respectively. In Leuven HRD status positive tumors, the median PFS was 44.8 months in the olaparib group and 20.7 months in the placebo group (HR 0.386; 95% CI 0.271–0.548) (Figure 1). The HR for Myriad test in this group was 0.373. In Leuven HRD score positive BRCA wild-type tumors, the median PFS was 31.1 months with olaparib and 18.6 months with placebo (HR 0.455; 95% CI 0.281–0.738). The HR for Myriad test was 0.407 in this group. 35% (n=164) of the samples were HRP with the Leuven test compared to 39% (n=182) with Myriad test. [Display omitted] Conclusions: A robust correlation between the Leuven HRD and Myriad myChoice PLUS test was observed. The Leuven HRD test showed in the PAOLA-1 trial a similar impact on PFS as the Myriad test. Subgroup analyses confirmed the PFS benefit with olaparib in patients with Leuven test BRCAm and HRD-positive/BRCAwt tumors. [ABSTRACT FROM AUTHOR]