Clinical evaluation of a low-coverage whole-genome test for detecting homologous recombination deficiency in ovarian cancer.

Autor:	Boidot R; Unit of Molecular Biology, Department of Biology and Pathology of Tumors, Georges-François Leclerc Cancer Center - UNICANCER, Dijon, France., Blum MGB; SeqOne Genomics, Montpellier, France. Electronic address: michael.blum@seqone.com., Wissler MP; CYPATH, Villeurbanne, France., Gottin C; SeqOne Genomics, Montpellier, France., Ruzicka J; SeqOne Genomics, Montpellier, France., Chevrier S; Unit of Molecular Biology, Department of Biology and Pathology of Tumors, Georges-François Leclerc Cancer Center - UNICANCER, Dijon, France., Delhomme TM; SeqOne Genomics, Montpellier, France., Audoux J; SeqOne Genomics, Montpellier, France., Jeanniard A; Agilent Technologies France, Les Ulis, France., Just PA; APHM (Assistance Publique - Hôpitaux de Marseille), Service de Pathologie Hôpitaux et services de santé, Marseille, Provence-Alpes-Côte d'Azur, France., Harter P; Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany., Pignata S; Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, and Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO), Naples, Italy., González-Martin A; Clinica Universidad de Navarra,GEICO, Madrid, Spain., Marth C; Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria., Mäenpää J; Tampere University Hospital, Department of Obstetrics and Gynecology, Finland., Colombo N; University of Milan-Bicocca and European Institute of Oncology IRCCS, Milan, Italy., Vergote I; University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium, European Union., Fujiwara K; Saitama Medical University International Medical Center, Saitama, Japan., Duforet-Frebourg N; SeqOne Genomics, Montpellier, France., Bertrand D; SeqOne Genomics, Montpellier, France., Philippe N; SeqOne Genomics, Montpellier, France., Ray-Coquard I; Centre Léon BERARD, and University Claude Bernard Lyon I, Lyon and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Lyon, France., Pujade-Lauraine E; Association de Recherche Cancers Gynécologiques (ARCAGY-GINECO), Paris, France.
Jazyk:	angličtina
Zdroj:	European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 May; Vol. 202, pp. 113978. Date of Electronic Publication: 2024 Mar 02.
DOI:	10.1016/j.ejca.2024.113978
Abstrakt:	Background: The PAOLA-1/ENGOT-ov25 trial showed that maintenance olaparib plus bevacizumab increases survival of advanced ovarian cancer patients with homologous recombination deficiency (HRD). However, decentralized solutions to test for HRD in clinical routine are scarce. The goal of this study was to retrospectively validate on tumor samples from the PAOLA-1 trial, the decentralized SeqOne assay, which relies on shallow Whole Genome Sequencing (sWGS) to capture genomic instability and targeted sequencing to determine BRCA status. Methods: The study comprised 368 patients from the PAOLA-1 trial. The SeqOne assay was compared to the Myriad MyChoice HRD test (Myriad Genetics), and results were analyzed with respect to Progression-Free Survival (PFS). Results: We found a 95% concordance between the HRD status of the two tests (95% Confidence Interval (CI); 92%-97%). The Positive Percentage Agreement (PPA) of the sWGS test was 95% (95% CI; 91%-97%) like its Negative Percentage Agreement (NPA) (95% CI; 89%-98%). In patients with HRD-positive tumors treated with olaparib plus bevacizumab, the PFS Hazard Ratio (HR) was 0.38 (95% CI; 0.26-0.54) with SeqOne assay and 0.32 (95% CI; 0.22-0.45) with the Myriad assay. In patients with HRD-negative tumors, HR was 0.99 (95% CI; 0.68-1.42) and 1.05 (95% CI; 0.70-1.57) with SeqOne and Myriad assays. Among patients with BRCA-wildtype tumors, those with HRD-positive tumors, benefited from olaparib plus bevacizumab maintenance, with HR of 0.48 (95% CI: 0.29-0.79) and of 0.38 (95% CI: 0.23 to 0.63) with the SeqOne and Myriad assay. Conclusion: The SeqOne assay offers a clinically validated approach to detect HRD. Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Declaration of interest of the paper entitled “Clinical evaluation of a low-coverage whole-genome test for detecting homologous recombination deficiency in ovarian cancer”. D. Bertrand, N. Duforet, C. Gottin, N. Philippe, and J. Ruzicka have filed a patent application with the European Patent Office on June 24, 2022 (application number EP 22181091.4) and an international patent application with the WIPO on June 23, 2023 (application number PCT/EP2023/067179), entitled "DEVICE FOR DETERMINING AN INDICATOR OF PRESENCE OF HRD IN A GENOME OF A SUBJECT". M. Blum, C. Gottin, J. Ruzicka, T. Delhomme, J. Audoux, N. Duforet-Frebourg, D. Bertrand, N. Philippe are employees of SeqOne Genomics. M.-P. Wissler is employed by Cypath. She received consulting fees from AstraZeneca and she was a speaker for seminars sponsored by Amgen, AstraZeneca, MSD, Roche, and Servier. A. Jeanniard is employed by Agilent. E. Pujade Lauraine was a member of advisory boards for AstraZeneca, GSK, and Roche. He was on the IDMC board at Agenus and Incyte. He is employed by ARCAGY-research. I. Vergote discloses financial relationships with Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, Zentalis, Oncoinvent AS, Amgen, Roche, Karyopharm, Genmab, Novocure. A. J. Gonzalez Martin discloses financial relationship with Alkermes, Amgen, Astrazeneca, Clovis, Eisai, Genmab, Gsk, Hederadx, Illumina, Inmunogen, Macrogenics, Mersana, MSD, Novartis, Novocure, Oncoinvent, Pharmamar, Regeneron, Roche, Sotio, Sutro, Takeda, Zaylab. He has also non-financial relationships with Aravive, GSK, MSD, Novartis, and Roche. N. Colombo received Grants or contracts from AstraZeneca, PharmaMar and Roche. She received payment or honoraria for lectures, presentations, or educational events from AstraZeneca, Tesaro, Novartis, Clovis Oncology, Merck Sharp and Dohme, GlaxoSmithKline and Eisai. She participated on a Data Safety Monitoring Board or Advisory Board for Roche, PharmaMar, AstraZeneca, Clovis Oncology, Merck Sharp and Dohme, GlaxoSmithKline, Tesaro, Pfizer, BioCad, Immunogen, Mersana, Eisai, Oncxema and Nuvation Bio. P. Alexandre received paid honoraria from GSK and Roche. K. Fujiwara received consulting fees and grant support from Pfizer, Eisai, Merck Sharp & Dohme, Taiho, Zeria, Chugai Pharmaceutical, Genmab, and Takeda Pharmaceutical Company, receiving grant support from Immunogen, Oncotherapy, and Regeneron, and receiving consulting fees from Novartis, Kyowa Hakko Kirin, Daiichi Sankyo, Mochida Pharmaceutical, and NanoCarrier. J. Mäenpää received honoraria from AstraZeneca and GSK. K. Fujiwara received consulting fees and grant support from Pfizer, Eisai, Merck Sharp & Dohme, Taiho, Zeria, Chugai Pharmaceutical, Genmab, Takeda Pharmaceutical Company, Novartis, Kyowa Hakko Kirin, Daiichi Sankyo, Mochida Pharmaceutical, and NanoCarrier, and received a grant support from Immunogen, Oncotherapy, and Regeneron. P. Harter discloses grant supports from AstraZeneca, Roche, GSK, Genmab, DFG, European Union, DKH, Immunogen, Clovis. He did consulting activities for AstraZeneca. He was a member of advisory councils for AstraZeneca, Roche, GSK, Clovis, Immunogen, MSD, and Eisai. He did lectures for Amgen, AstraZeneca, GSK, Roche, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai. All remaining authors have declared no conflicts of interest. (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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