Homologous recombination deficiency in ovarian cancer: Global expert consensus on testing and a comparison of companion diagnostics.

Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Competing Interests: Declaration of Competing Interest Stanislas Quesada: Honoraria for lectures: GSK, AZ . Honoraria for advisory boards: GSK. Reimbursement for travel expenses: GSK, AZ, MSD, EISAI. Frédérique Penault-Llorca: Personal honoraria: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Clovis, EISAI, Exact Science, GSK, Illumina, Invitae, Lilly, MSD, Myriad, Novartis, Pfizer, Pierre-Fabre, Roche, Sanofi, Veracyte. Funding to institution for translational research: AbbVie, Astellas, AstraZeneca, Bayer, BMS, Genomic Health, Illumina, Lilly, MSD, Myriad, Nanostring, Novartis, Pfizer, Pierre-Fabre, Roche. Travel grants: AbbVie, AstraZeneca, Bayer, BMS, Gilead, MSD, Novartis, Pfizer, Roche. Xavier Matias-Guiu: Personal fees as an invited speaker: Roche Farma, Qiagen, Ferrer Internacional, Novartis, Menarini, Biocartis, Agilent-Dako, Leyca, Reig Jofre, Sysmex, MSD, Astra-Zeneca, BMS, GSK, Clovis; Advisory Boards: Astra-Zeneca, Lilly, Amgen, GSK, Janssen, Illumina, MSD. Susana Banerjee: Personal fees for advisory board membership from, AstraZeneca, Eisai, Epsilogen, GSK, ImmunoGen, Mersana, MSD, Myriad, Novartis, Oncxerna, Regeneron, Roche, Seagen, Shattuck Labs and Verastem; personal fees as an invited speaker from Abbvie, AstraZeneca , GSK, Medscape, Novacure, Peerview, Pfizer, Research to Practice and Takeda; travel expenses Verastem, AstraZeneca, GSK. Ownership of stocks/shares of PerciHealth; institutional research grants from AstraZeneca and GSK; a non-remunerated role as a PI for AstraZeneca (academic-sponsored ENGOT-GYN1/ATARI phase II international trial), GSK (academic-sponsored MONITOR-UK trial) and Verastem (ENGOTov60/GOG3052/RAMP201 phase II clinical trial – global lead); a non-remunerated leadership role as board member of the International Cancer Foundation; and a non-renumerated advisory role as a medical advisor of Ovacome Charity. Massimo Barberis: Honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, expenses from MSD Oncology, Roche/Genetech, AstraZeneca, GSK, Amgen, Thermofisher Scientifics and Illumina. Robert L. Coleman: Grants/contracts: AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Roche/Genentech, Karyopharm; consulting fees from: Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, OncoQuest, Onxerna, Regeneron, Karyopharm, Roche/Genentech, Novocure, Merck, Abbvie, Novocure; honoraria from lectures: AstraZeneca, Clovis, Roche/Genentech, Merck. Nicoletta Colombo: Personal fees for advisory board membership from AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris and Roche, Novocure; personal fees as an invited speaker from AstraZeneca and Novartis; institutional research grants from AstraZeneca, PharmaMar and Roche; a non-renumerated membership of the ESMO Guidelines Steering Committee; and a non-renumerated leadership role as Chair of the Alleanza Contro il Tumore Ovarico (ACTO) Scientific Committee. Anna DeFazio: Research grant support from AstraZeneca and Illumina. Consumer survey advisory committee, Verastem. Iain A. McNeish: Personal honoraria for advisory boards for AstraZeneca, GSK, Clovis Oncology, BioNTech, Roche, Episila Bio and OncoC4. Travel, accommodation and/or expenses from GSK, BioNTech and AstraZeneca. Institutional grant support from AstraZeneca. Angélica Nogueira-Rodrigues: Personal honoraria for advisory boards from Abbvie, AstraZeneca, Daiichi Sankyo, Eisai, Gilead, GSK, Immunogen, MSD, Novartis, Pfizer, Roche. President-elect for the Brazilian Society of Medical Oncology (not recompensed); Chair LACOG (not recompensed); Director of strategic planning Brazilian Group of Gynecologic Cancer (not recompensed). Ana Oaknin: Personal fees for advisory board membership from: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daiichi Sankyo, Debiopharm International, Eisai, Exelisis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, Inc., PharmaMar, Regeneron, Sattucklabs, Seagen/Pfizer, Sutro Biopharma and Zentalis; personal fees for travel/accommodation from: AstraZeneca, PharmaMar, Roche. Sandro Pignata: Honoraria from MSD, AstraZeneca, GSK, Roche, Novartis, Pharmamar; Research funding from AstraZeneca, MSD, Roche, GSK, Pfizer. Éric Pujade-Lauraine: Personal honoraria for advisory boards/IDMC from Agenus, AstraZeneca, GSK, Incyte, MSD, Roche. Employee ARCAGY. Étienne Rouleau: served in a consulting/advisory role for AstraZeneca, Roche Diagnostics, Clovis, GSK, and BMS, and has received travel/accommodation expenses from AstraZeneca and BMS. Aleš Ryška: Honoraria for advisory services and invited lectures: Amgen, AstraZeneca, BMS, Eli-Lilly, Janssen-Cilag, MSD, Roche, Gilead, Novartis, Sanofi, Merck Serono, Bayer. Travel support: Gilead, Sanofi. Immediate past president of the European Society of Pathology (not recompensed). Nerina Van Der Merwe: Travel and accommodation expenses from AstraZeneca, Roche and Gknowmix. Toon Van Gorp: Institutional honoraria for advisory boards from AstraZeneca, BioNTech, Eisai, GSK, ImmunoGen, Incyte, MSD, OncXerna Therapeutics, Seagen, Tubulis, Zentalis. Travel, accommodation, and/or expenses from AstraZeneca, GSK, ImmunoGen, MSD, and PharmaMar. Research funding from Amgen, AstraZeneca, and Roche. Chair of BGOG (not recompensed). Ignace Vergote: Consulting Ad Boards: Akesobio, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, ITM, Jazzpharma, Karyopharm, MSD, Novocure, Oncoinvent, Sanofi, Regeneron, Seagen, Sotio, Zentalis; Consulting Data monitoring Committees: Agenus, AstraZeneca, Corcept, Exelixis, F. Hoffmann-La Roche, Immunogen, Kronos Bio, Mersana, Novartis, OncXerna, Verastem Oncology. Wilko Weichert: Honoraria: Boehringer Ingelheim, Janssen, Roche, MSD, Bristol-MyersSquibb, AstraZeneca, Pfizer, Merck KGaA, Lilly, Novartis, Takeda, Bayer, Amgen, Astellas Pharma, Illumina, Eisai, Siemens, Agilent, ADC Therapeutics, GlaxoSmithKline, MolecularHealth Consulting or Advisory Role: Roche, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Merck KGaA, AstraZeneca, Novartis, Boehringer Ingelheim, Agilent, Illumina, MolecularHealth, Siemens Healthcare Diagnostics, ADC Therapeutics, Astellas Pharma, Janssen, Eisai, Takeda, GlaxoSmithKline, Lilly, Amgen, Bayer. Speakers’ Bureau: Lilly, Amgen, Merck Sharp & Dohme, Pfizer, Bristol Myers Squibb, Roche, Novartis, Johnson & Johnson/Janssen, Eisai, AstraZeneca/MedImmune, Takeda, Agilent, Siemens, Astellas Pharma, Illumina, Roche, Bayer, MolecularHealth, ADC Therapeutics, Merck, Boehringer Ingelheim. Research Funding: Roche (Inst), Bristol Myers Squibb (Inst), Merck Sharp & Dohme (Inst), AstraZeneca/MedImmune (Inst). Travel, Accommodations, Expenses: Roche, Bayer, Bristol Myers Squibb, MSD, AstraZeneca, ADC Therapeutics, Astellas Pharma, MolecularHealth, Siemens, Novartis, Illumina, Agilent, Takeda, Eisai, GlaxoSmithKline, Merck, Boehringer Ingelheim, AstraZeneca, Lilly, Janssen, Pfizer. Xiaohua Wu: No potential conflicts of interest. Isabelle Ray-Coquard: Personal honoraria for advisory boards from Abbvie, Adaptimmune, Agenus, Amgen, AstraZeneca, BMS, Clovis, Corsett, Daiichi Sankyo, Deciphera, Eisai, EQRX, GSK, Immunogen, Immunocore, Merck Serono, MacroGenics, MSD, Mersana, Novartis, Onxeo, PharmaMar, Roche, Sutro Biopharma, Zentalis; Honorarium to institution for advisory boards from MSD (translational research); Funding to institution for translational research from BMS; President of GINECO (not recompensed); Chair-elect of ENGOT (not recompensed). Pascal Pujol: Consulting fees from Exact Science; Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, HEDERADx, MSD, Novartis, Onco DNA, Predilife, and Seqone.
(Copyright © 2024. Published by Elsevier Ltd.)