Shallow whole genome sequencing approach to detect Homologous Recombination Deficiency in the PAOLA-1/ENGOT-OV25 phase-III trial.

Autor: Callens C; Genetics Laboratory, Department of Diagnostic and Theranostic Medicine, Institut Curie and Paris Sciences Lettres Research University, Paris, France. celine.callens@curie.fr., Rodrigues M; Medical Oncology Department, Institut Curie and Paris Sciences Lettres Research University, Paris, France.; Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) Team, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Briaux A; Genetics Laboratory, Department of Diagnostic and Theranostic Medicine, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Frouin E; Clinic Bioinformatics Unit, Department of Diagnostic and Theranostic Medicine, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Eeckhoutte A; Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) Team, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Pujade-Lauraine E; ARCAGY Research, Paris, France., Renault V; Clinic Bioinformatics Unit, Department of Diagnostic and Theranostic Medicine, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Stoppa-Lyonnet D; Genetics Laboratory, Department of Diagnostic and Theranostic Medicine, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Bieche I; Genetics Laboratory, Department of Diagnostic and Theranostic Medicine, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Bataillon G; Department of Pathology, University Cancer Institute of Toulouse-Oncopole, Toulouse, France., Karayan-Tapon L; Biology of Cancer laboratory, University Hospital of Poitiers, Poitiers, France., Rochelle T; Biology of Cancer laboratory, University Hospital of Poitiers, Poitiers, France., Heitz F; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.; Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, and AGO, Berlin, Germany., Cecere SC; Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, and MITO, Napoli, Italy., Pérez MJR; Hospital Reina Sofia, Cordoba, and GEICO Group, Córdoba, Spain., Grimm C; Division of General Gynecology and Gynecologic Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, and AGO Austria, Vienna, Austria., Nøttrup TJ; Department of Oncology, Copenhagen University Hospital-Rigshospitalet and NSGO, Copenhagen, Denmark., Colombo N; Dipartimento Medicina e Chirurgia, Università Milano-Bicocca, Istituto Europeo Oncologia, Milano, and MaNGO, Milano, Italy., Vergote I; University Hospital Leuven, Leuven Cancer Institute, and BGOG, Leuven, Belgium., Yonemori K; Department of Medical Oncology, National Cancer Center Hospital, Tokyo, and GOTIC, Tokyo, Japan., Ray-Coquard I; Centre Léon BERARD, and University Claude Bernard Lyon I, Lyon, and GINECO, Lyon, France., Stern MH; Genetics Laboratory, Department of Diagnostic and Theranostic Medicine, Institut Curie and Paris Sciences Lettres Research University, Paris, France.; Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) Team, Institut Curie and Paris Sciences Lettres Research University, Paris, France., Popova T; Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) Team, Institut Curie and Paris Sciences Lettres Research University, Paris, France.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2023 Nov; Vol. 42 (48), pp. 3556-3563. Date of Electronic Publication: 2023 Nov 09.
DOI: 10.1038/s41388-023-02839-8
Abstrakt: The bevacizumab (bev)/olaparib (ola) maintenance regimen was approved for BRCA1/2-mutated (BRCAmut) and Homologous Recombination Deficient (HRD) high-grade Advanced Ovarian Cancer (AOC) first line setting, based on a significantly improved progression-free survival (PFS) compared to bev alone in the PAOLA-1/ENGOT-ov25 trial (NCT02477644), where HRD was detected by MyChoice CDx PLUS test. The academic shallowHRDv2 test was developed based on shallow whole-genome sequencing as an alternative to MyChoice. Analytical and clinical validities of shallowHRDv2 as compared to MyChoice on 449 PAOLA-1 tumor samples are presented. The overall agreement between shallowHRDv2 and MyChoice was 94% (369/394). Less non-contributive tests were observed with shallowHRDv2 (15/449; 3%) than with MyChoice (51/449; 11%). Patients with HRD tumors according to shallowHRDv2 (including BRCAmut) showed a significantly prolonged PFS with bev+ola versus bev (median PFS: 65.7 versus 20.3 months, hazard ratio (HR): 0.36 [95% CI: 0.24-0.53]). This benefit was significant also for BRCA1/2 wild-type tumors (40.8 versus 19.5 months, HR: 0.45 [95% CI: 0.26-0.76]). ShallowHRDv2 is a performant, clinically validated, and cost-effective test for HRD detection.
(© 2023. The Author(s).)
Databáze: MEDLINE
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