Homologous Recombination Repair Deficiency (HRD) Testing in Newly Diagnosed Advanced-stage Epithelial Ovarian Cancer in Italy

In 2024, approximately 5,423 new cancer diagnoses were estimated in Italy. The centers participating in this study collectively manage about 40-50% of all ovarian cancer cases diagnosed annually in the country, offering a robust and representative snapshot of national clinical practice and treatment patterns.

The promoting center has also been recognized as a referral center for ovarian cancer treatment by the European Society of Gynecologic Oncology, based on the number of patients treated and the quality of treatment parameters. HRD testing is recommended at diagnosis for patients with HGOC, in line with NCCN (ref) and ESMO guidelines (ref), so that treatment decisions, particularly the use of PARP inhibitors, can be informed early in the clinical pathway. Several commercial assays are available, each adopting different approaches to evaluate genomic instability.

Although HRD testing is central to guiding treatment decisions in HGOC, its implementation remains challenging and subject to laboratory variability in methodology and interpretation. Real-world evidence on how frequently HRD results influence clinical management and how these results correlate with other patient or disease characteristics is still limited. This study aims to collect detailed information on patients tested in referral laboratories in Italy and the impact of HRD status on therapeutic choices.

A retrospective analysis will be conducted on a multicenter cohort of HGOC patients who consecutively underwent HRD testing. Since the participating centers treat a substantial proportion of FIGO 2014 stage III-IV HGOC cases nationwide, the study provides an indirect estimate of HRD testing uptake in clinical practice.

Study design: Multicenter (n=7), observational, retrospective, non-profit study co-funded by Astrazeneca Spa Data Source(s): Data will be collected in all participating centers through a GDPR compliant electronic form.

Study Population: 1125 advanced (FIGO stage 2014 III-IV) HGOC patients addressed to HRD testing at multiple centers.

Outcome(s):

Main outcomes include:

1. Prevalence of HRD-positive tumors; 2. Association between HRD status and key baseline clinical characteristics; 3. Treatment choices following HRD determination;

Secondary endpoints include:

1. Turn-around-time (TAT) for HRD report; 2. Assay feasibility and reportability; 3. Correlation between HRD score and continuous clinical measures; 4. Time-to-event exploratory prognostic outcomes by HRD status (exploratory).

Sample Size Estimations:

Based on an expected HRD positivity rate of 40% among EOC patients, an effective sample size of approximately 1,046 patients (accounting for a 7% drop-out from an initial cohort of 1,125 patients) will allow us to estimate the prevalence with a 95% confidence interval of ±3%. Additionally, this sample size provides over 80% power to detect a 10% difference in HRD positivity rates between subgroups (e.g. different test types) at a significance level of 0.05. Therefore, the proposed sample size is sufficient to achieve the study's objectives and will provide statistically robust and clinically meaningful insights into HRD testing practices in Italy.