卵巢癌同源重组缺陷（HRD）检测：一项法国多中心II期研究（HERO）

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

作者信息

Leman Raphaël, Cherifi François, Leheurteur Marianne, Theret Pierrick, Pasquesoone Camille, Saint-Ghislain Mathilde, Bresson Lucie, Denoyelle Christophe, Vigneron Nicolas, Poulain Laurent, Delepee Raphaël, Berby Benoit, Dremaux Julie, Dumont Aurélie, Blanc-Fournier Cécile, Jeanne Corinne, Briand Mélanie, Rousseau Nathalie, Pepin Louis-Ferdinand, Deruche Elodie, Dumont Fabienne, Leconte Alexandra, Lequesne Justine, Clarisse Bénédicte, Joly Florence, Castera Laurent, Rouzier Roman

机构信息

Laboratoire de Biologie et de génétique du Cancer, Comprehensive Cancer Center François Baclesse, UNICANCER, 3 avenue Général Harris, Caen, 14000, France.

Cancer and Brain Genomics, Inserm UMR1245, Normandy University, Rouen, 76000, France.

出版信息

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

DOI:10.1186/s12885-025-14423-2

PMID:40597907

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12210802/

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.

摘要

背景

同源重组缺陷（HRD）肿瘤的鉴定目前是卵巢癌治疗管理的关键步骤。HRD肿瘤对奥拉帕利维持治疗和铂类化疗均敏感。尽管目前有大量的HRD检测方法，但只有少数HRD检测方法在卵巢癌患者的临床队列中得到了前瞻性验证。为应对这些挑战，我们实验室最近开发了一种名为GIScar（基因组不稳定疤痕）的HRD检测方法。我们的HRD检测方法在PAOLA-1临床试验的回顾性队列中成功验证了对肿瘤对奥拉帕利敏感性的预测。然而，我们尚未在前瞻性临床队列中验证GIScar。

方法

HERO试验是一项非随机多中心II期研究，旨在前瞻性验证GIScar检测方法在新诊断的高级别浆液性卵巢癌（HGSOC）患者中的应用。主要终点是铂敏感患者的比例（一线化疗后的敏感性）。铂敏感性定义为根据RECIST 1.1标准，在一线铂类化疗后六个月没有疾病进展的患者（根据GIScar HRD状态）。次要终点包括GIScar和MyChoice CDx（由Myriad Genetics提供）检测方法的比较、根据HRD状态评估生存率以及测量CA-125浓度动力学（KELIM）。对于符合条件的入组患者，将进行两种HRD检测：GIScar检测和MyChoice CDx检测。患者将按照常规做法接受一线铂类化疗，联合或不联合贝伐单抗。根据目前对至少一项HRD检测呈阳性的患者的建议，将给予PARP抑制剂奥拉帕利进行维持治疗。我们计划总共招募88名患者。患者将在入组后随访48个月。