The study aims to provide a comprehensive overview of HRD testing practices for 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.
Study Type
OBSERVATIONAL
Enrollment
1,125
HRD testing on FFPE samples
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Italy
Association between HRD status and key baseline clinical characteristics
Comparison of the percentage of patients with HRD-positive versus HRD-negative status according to key baseline clinical and pathological characteristics, including disease stage at initial diagnosis (I-IV), histological subtype, patterns of metastatic spread, and type of prior lines of therapy. Biomarker profiles, including BRCA mutation status, will also be compared when available. Clinical and pathological characteristics will be assessed using medical records, pathology reports, and available molecular/genomic testing results.
Time frame: Through study completion, an average of 1 year
Treatment choices following HRD determination
Percentage of patients receiving each type of maintenance therapy following HRD testing, including PARP inhibitor monotherapy or combination therapy with bevacizumab. Treatment information will be obtained from medical records.
Time frame: Through study completion, an average of 1 year
Turn-around-time (TAT) for HRD report
The interval from surgery to finalized HRD report will be measured in calendar days to gauge the practicality of integrating HRD testing into routine care
Time frame: Through study completion, an average of 1 year
Proportion of Samples With a Valid, Reportable HRD Assay Result
The proportion of samples generating a valid, reportable HRD assay result will be calculated as the number of samples with a valid, reportable HRD assay result divided by the total number of samples submitted for HRD testing.
Time frame: Through study completion, an average of 1 year
Correlation between HRD score and continuous clinical measures
Where HRD scores are available as continuous values, we will examine their associations with continuous baseline clinical variables (e.g., patient age and tumor-burden proxies such as baseline CA-125 levels) using simple linear regression models. This approach will allow estimation of the direction and magnitude of associations and assessment of linear trends across the range of HRD scores.
Time frame: Through study completion, an average of 1 year
Time-to-event exploratory prognostic outcomes by HRD status (exploratory)
To generate hypotheses for future studies, progression-free survival (PFS) and overall survival (OS) will be analyzed according to HRD status. These exploratory time-to-event analyses aim to provide preliminary insights into whether HRD positivity confers prognostic or predictive value beyond immediate treatment choice
Time frame: Through study completion, an average of 1 year
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