Quesada Stanislas, Penault-Llorca Frédérique, Matias-Guiu Xavier, Banerjee Susana, Barberis Massimo, Coleman Robert L, Colombo Nicoletta, DeFazio Anna, McNeish Iain A, Nogueira-Rodrigues Angélica, Oaknin Ana, Pignata Sandro, Pujade-Lauraine Éric, Rouleau Étienne, Ryška Aleš, Van Der Merwe Nerina, Van Gorp Toon, Vergote Ignace, Weichert Wilko, Wu Xiaohua, Ray-Coquard Isabelle, Pujol Pascal
Department of Medical Oncology, Institut régional du Cancer de Montpellier (ICM), Montpellier, France; Department of Cancer Genetics, University Hospital of Montpellier, Montpellier, France; Groupe d'Investigateurs Nationaux pour l'Etude des cancers de l'ovaire et du sein (GINECO), Paris, France; Société Française de Médecine Prédictive et Personnalisée (SFMPP), Montpellier, France.
Société Française de Médecine Prédictive et Personnalisée (SFMPP), Montpellier, France; Department of Biology and Pathology, Centre de Lutte Contre le Cancer Jean Perrin, Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, UMR 1240 INSERM-UCA, Clermont-Ferrand, France; Cours St Paul, Saint Paul, Réunion, France.
Eur J Cancer. 2025 Jan 17;215:115169. doi: 10.1016/j.ejca.2024.115169. Epub 2024 Dec 9.
Poly (ADP ribose) polymerase inhibitors (PARPis) are a treatment option for patients with advanced high-grade serous or endometrioid ovarian carcinoma (OC). Recent guidelines have clarified how homologous recombination deficiency (HRD) may influence treatment decision-making in this setting. As a result, numerous companion diagnostic assays (CDx) have been developed to identify HRD. However, the optimal HRD testing strategy is an area of debate. Moreover, recently published clinical and translational data may impact how HRD status may be used to identify patients likely to benefit from PARPi use. We aimed to extensively compare available HRD CDx and establish a worldwide expert consensus on HRD testing in primary and recurrent OC.
A group of 99 global experts from 31 different countries was formed. Using a modified Delphi process, the experts aimed to establish consensus statements based on a systematic literature search and CDx information sought from investigators, companies and/or publications.
Technical information, including analytical and clinical validation, were obtained from 14 of 15 available HRD CDx (7 academic; 7 commercial). Consensus was reached on 36 statements encompassing the following topics: 1) the predictive impact of HRD status on PARPi use in primary and recurrent OC; 2) analytical and clinical validation requirements of HRD CDx; 3) resource-stratified HRD testing; and 4) how future CDx may include additional approaches to help address unmet testing needs.
This manuscript provides detailed information on currently available HRD CDx and up-to-date guidance from global experts on HRD testing in patients with primary and recurrent OC.
聚（ADP核糖）聚合酶抑制剂（PARPis）是晚期高级别浆液性或子宫内膜样卵巢癌（OC）患者的一种治疗选择。最近的指南已经阐明了同源重组缺陷（HRD）在这种情况下如何影响治疗决策。因此，已经开发了许多伴随诊断检测（CDx）来识别HRD。然而，最佳的HRD检测策略仍是一个有争议的领域。此外，最近发表的临床和转化数据可能会影响HRD状态如何用于识别可能从PARPi治疗中获益的患者。我们旨在广泛比较现有的HRD CDx，并就原发性和复发性OC的HRD检测达成全球专家共识。
组建了一个由来自31个不同国家的99名全球专家组成的小组。专家们采用改进的德尔菲法，旨在基于系统的文献检索以及从研究者、公司和/或出版物中获取的CDx信息制定共识声明。
从15种可用的HRD CDx中的14种（7种学术性；7种商业性）获得了包括分析和临床验证在内的技术信息。就36项声明达成了共识，这些声明涵盖以下主题：1）HRD状态对原发性和复发性OC中PARPi使用的预测影响；2）HRD CDx的分析和临床验证要求；3）资源分层的HRD检测；4）未来的CDx如何可能包括其他方法以帮助满足未满足的检测需求。
本手稿提供了有关当前可用的HRD CDx的详细信息，以及全球专家关于原发性和复发性OC患者HRD检测的最新指南。
