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).
Shash et al. (Wed,) studied this question.