1. Homologous recombination deficiency should be tested for in patients with advanced stage high-grade serous ovarian cancer aged 70 years and over.
- Author
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Pitiyarachchi O, Ansell PJ, Coleman RL, Dinh MH, Holman L, Leath CA 3rd, Werner T, DiSilvestro P, Morgan M, Tew W, Lee C, Cunningham M, Newton M, Edraki B, Lim P, Barlin J, Spirtos NM, Tewari KS, Edelson M, Reid T, Carlson J, and Friedlander M
- Subjects
- Humans, Female, Aged, Middle Aged, BRCA2 Protein genetics, Aged, 80 and over, Age Factors, Adult, Homologous Recombination, Neoplasm Staging, Neoplasm Grading, Genetic Testing methods, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous pathology, BRCA1 Protein genetics
- Abstract
Objective: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group., Methods: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed)., Results: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36)., Conclusions: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications., Competing Interests: Declaration of competing interest The following authors have no disclosures relating to this manuscript: Omali Pitiyarachchi, Laura Holman, Paul DiSilvestro, Mark Morgan, William Tew, Christine Lee, Meredith Newton, Babak Edraki, Thomas Reid and Jay Carlson. Peter J. Ansell and Minh H Dinh are AbbVie employees receiving stock or stock options. Robert L. Coleman: has received grants or contracts from 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; royalties or licenses with Up-To-Date; payment or honoraria for speakers bureaus from AstraZeneca, Clovis, Roche/Genentech, Merck; participation in data safety monitoring or advisory boards from NRG Oncology, Elsai/BMS; leadership or fiduciary role in Onxeo/Valerio, Vaniam Group, GOG Foundation, International Gynecologic Cancer Society, OCNA, Ovarcome. Charles A. Leath III: Grant to institution provided by National Institutes of Health (NCI UG1 CA233330). Theresa Werner has received consulting fees from Mersana; and research funding to the institution - AbbVie, Acrivon, Astra Zeneca, BluePrint, Clovis Oncology, Genmab, GSK-Tesaro, Mersana, Repare Therapeutics, Roche-Genentech. Mary Cunningham: funds to institution provided by Abbvie, AstraZeneca, Clovis Oncology, Tesaro, Vascular Biogenics; and spouse is a stockholder of Intuitive Surgical. Peter Lim: has received payment or honoraria for Speakers Bureau from Astra Zeneca and Merck and is on Advisory Boards for Astra Zeneca, Clovis, Mersana, OncoC4, Immunogen. Joyce Barlin: has received payment/honoraria for Speakers Bureaus from Astra Zeneca and Merck and is on Advisory Boards for Astra Zeneca, Clovis, Mersana, OncoC4, Immunogen. Nicola M. Spirtos: has received institutional grants from NRG and the GOG Foundation. Krishnansu S. Tewari: reports grants to institution (UC Irvine) provided by AbbVie; consulting fees from Merck, Astra Zeneca, Eisai, Seagen, GSK; and payment/honoraria for Speakers Bureaus from Merck, Astra Zeneca, Eisai, Seagen, GSK. Mitchell Edelson: has received funding to attend meetings from Intuitive Surgical; received stock options from Merck when employed. Spouse was a salaried employee at Merck until 8/2022 and spouse is a salaried employee at Pfizer since 3/2023. Michael Friedlander: has received consulting fees from Astra Zeneca, Novartis and GSK; has consulted without payment for Incyclix; has received payment or honoraria for Speakers Bureaus from Astra Zeneca, GSK and MSD; has participated on Data Safety Monitoring or Advisory Boards for AGITG IDSMB and ENDO-3; received institutional support in the form of research grants from Astra Zeneca, Beigene and Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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