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Clinical Trial
. 2025 Jul 1;25(1):1075.
doi: 10.1186/s12885-025-14423-2.

Homologous recombination deficiency (HRD) tests for ovarian cancer: a multicenter French phase II study (HERO)

Raphaël Leman  1   2 , François Cherifi  3 , Marianne Leheurteur  4 , Pierrick Theret  5 , Camille Pasquesoone  6 , Mathilde Saint-Ghislain  6 , Lucie Bresson  6 , Christophe Denoyelle  7   8 , Nicolas Vigneron  7   8   9 , Laurent Poulain  7   8 , Raphaël Delepee  7   8   10 , Benoit Berby  11 , Julie Dremaux  12 , Aurélie Dumont  13 , Cécile Blanc-Fournier  14 , Corinne Jeanne  14 , Mélanie Briand  7   8 , Nathalie Rousseau  15 , Louis-Ferdinand Pepin  16 , Elodie Deruche  17 , Fabienne Dumont  18 , Alexandra Leconte  19 , Justine Lequesne  19 , Bénédicte Clarisse  19 , Florence Joly  20 , Laurent Castera  21   22 , Roman Rouzier  23
Affiliations
Clinical Trial

Homologous recombination deficiency (HRD) tests for ovarian cancer: a multicenter French phase II study (HERO)

Raphaël Leman et al. BMC Cancer. .

Abstract

Background: The identification of homologous recombination deficient (HRD) tumor is now a crucial step for the therapeutic management of ovarian cancer. The HRD tumors are both sensitive to olaparib maintenance treatment and to platinum-based chemotherapy. Despite the large amount of HRD tests currently available, only a few HRD tests were prospectively validated on a clinical cohort of patients with ovarian cancer. To fulfil these challenges, our laboratory has recently developed a HRD test named GIScar (Genomic Instability Scar). Our HRD test was successfully validated on the retrospective cohort of PAOLA-1 clinical trial regarding the prediction of tumor sensitivity to olaparib. However, we have not yet validated GIScar on a prospective clinical cohort.

Methods: The HERO trial is a nonrandomized multicenter phase II study aiming to prospectively validate the GIScar test among patients with newly diagnosed high-grade serous ovarian cancer (HGSOC). The primary endpoint is the rate of platinum-sensitive patients (sensitivity after first line of chemotherapy). Platinum-sensitivity is defined as patients without absence of disease progression, according to RECIST 1.1 criteria, six months after a first-line platinum-based chemotherapy) according to GIScar HRD status. Secondary endpoints include the comparison of GIScar and MyChoice CDx (provided by Myriad Genetics®) tests, the assessment of survival according to the HRD status, and the measure of CA-125 concentration kinetic (KELIM). For eligible enrolled patients, two HRD tests will be performed: the GIScar test, and the MyChoice CDx test. Patients will receive a first-line platinum-based chemotherapy, with or without bevacizumab, as per routine practice. A maintenance treatment with olaparib, a PARP inhibitor, will be indicated according to current recommendations for patients with at least one positive HRD test. We plan to enroll 88 patients overall. Patients will be followed up to 48 months after inclusion.

Discussion: Use of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors and in particular ovarian cancer. Developing new assays is part of the missions of the molecular genetics platforms to improve accessibility and reduce cost compared to non-academic assays.

Trial registration: IDRCB 2023A0158540, ClinicalTrials.gov NCT06152731 (November 22, 2023).

Protocol version: Version 3.1 dated from 2024-10-23.

Keywords: Homologous recombination deficiency; Molecular biology; Ovarian cancer; Platinum resistance.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study has received ethical approval from the Comité de Protection des Personnes Ile de France IV in November 2023 (N° IDRCB 2023-A01585-40, Ref 23.03705.000286). All patients will be proposed to participate by medical oncologists, who will give them an information file. All patients will give their written informed consent before any study-related assessment start. This study will be performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the HERO study. GIScar: Genomic Instability Scar; LBGC: Laboratoire de biologie et de génétique du cancer (LBGC), Centre François Baclesse, Caen, France; HRP: homologous recombination (HR) proficient; HRD: HR deficient
See this image and copyright information in PMC

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