Homologous recombination deficiency in newly diagnosed advanced ovarian cancer across nine Middle East countries: prevalence, real-world testing pathways, and treatment implications

With current evidence of homologous recombination deficiency (HRD) emerging as a predictive and prognostic biomarker in high-grade serous/endometrioid ovarian cancers (HGSOC/HGEOC), the HALO study (NCT04991051) evaluated the prevalence of the HRD in patients with HGSOC/HGEOC, primary peritoneal cancer (PPC), and fallopian tube cancer (FTC) across Asia, Middle East and Africa (MEA), and Russia. The MEA subset of this cross-sectional, non-interventional study enrolled patients with newly diagnosed stage III/IV (International Federation of Gynaecology and Obstetrics [FIGO] classification) HGSOC/HGEOC, PPC, FTC during May 2021-Jan 2022 with formalin-fixed paraffin-embedded tumour block(s) collected within 120 days of enrolment. Primary endpoints included prevalence of HRD, genomic instability (GI) excluding tumour BRCA mutations (tBRCAm), and tBRCAm. Logistic regression model predicted the risk factors associated with HRD positivity and tBRCAm. Of 195 patients (median [range] age, 58.2 [24.0-89.0] years), 88.7% had primary ovarian tumour. The HRD status was analysed in 180 patients; 52.2% (94/180) were HRD positive – 23.9% (43/180) had high GI scores excluding tBRCA1/2m, and 28.3% (51/180) had tBRCAm. More than two-thirds (71.3%) of patients underwent debulking surgery, 45,1% received neoadjuvant and 50.8% received adjuvant therapy. No patients received PARPi therapy. In univariate analysis, nulliparity was associated with lower odds of HRD positivity (odds ratio [OR]: 0.27, p=0.003). Family history (OR: 0.39, p=0.02) and nulliparous women (OR: 0.19, p=0.03) were associated with lower odds of high GI score. Higher odds of tBRCAm were observed in ex-smokers (OR: 6.77, p=0.02), family history (OR: 3.11, p=0.0009), and surgically resected tissue (OR: 2.00, p=0.04); lower odds in patients with FIGO stage IV (OR: 0.26, p=0.004). In multivariate analysis, h/o genetic-related cancer (OR: 3.75, p=0.002), h/o contraceptive use (OR: 5.19, p=0.009) was associated with higher odds of tBRCA1m whereas FIGO stage IV disease (OR: 0.24, p=0.006) had lower odds of tBRCAm. In the Middle East subset of HALO study, a substantial proportion of patients were HRD positive and had tBRCA1/2m, supporting the clinical relevance of these biomarkers for guiding novel targeted therapies. The study provides real-world evidence of HRD and tBRCA prevalence, informing future research and policy development in precision oncology for the region. Number-NCT04991051 (Date of Approval-September 2020).