Shallow whole genome sequencing approach to detect Homologous Recombination Deficiency in the PAOLA-1/ENGOT-OV25 phase-III trial.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
31
05
2023
accepted:
11
09
2023
revised:
06
09
2023
medline:
27
11
2023
pubmed:
10
11
2023
entrez:
9
11
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37945748
doi: 10.1038/s41388-023-02839-8
pii: 10.1038/s41388-023-02839-8
pmc: PMC10673712
doi:
Substances chimiques
BRCA1 protein, human
0
BRCA1 Protein
0
BRCA2 protein, human
0
BRCA2 Protein
0
Types de publication
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3556-3563Informations de copyright
© 2023. The Author(s).
Références
JCO Precis Oncol. 2023 Jan;7:e2200258
pubmed: 36716415
Nature. 2005 Apr 14;434(7035):917-21
pubmed: 15829967
Bioinformatics. 2012 Feb 1;28(3):423-5
pubmed: 22155870
Nature. 2005 Apr 14;434(7035):913-7
pubmed: 15829966
Nat Genet. 2017 Oct;49(10):1476-1486
pubmed: 28825726
Nat Cancer. 2022 Oct;3(10):1181-1191
pubmed: 36253484
Nat Commun. 2017 Oct 11;8(1):857
pubmed: 29021619
Nat Cancer. 2022 Oct;3(10):1141-1143
pubmed: 36253485
Nat Rev Cancer. 2023 Feb;23(2):78-94
pubmed: 36471053
Lancet. 2017 Oct 28;390(10106):1949-1961
pubmed: 28916367
JAMA Oncol. 2022 Dec 1;8(12):1802-1808
pubmed: 36301572
Cancer Res. 2012 Nov 1;72(21):5454-62
pubmed: 22933060
J Natl Cancer Inst. 2021 Jul 1;113(7):917-923
pubmed: 33372675
Cancer Res. 2016 Apr 1;76(7):1882-91
pubmed: 26787835
Eur J Cancer. 2023 Jul;188:131-139
pubmed: 37245441
J Clin Oncol. 2022 Dec 1;40(34):3952-3964
pubmed: 35658487
Br J Cancer. 2012 Nov 6;107(10):1776-82
pubmed: 23047548
N Engl J Med. 2019 Dec 19;381(25):2416-2428
pubmed: 31851799
Bioinformatics. 2020 Jun 1;36(12):3888-3889
pubmed: 32315385
N Engl J Med. 2018 Dec 27;379(26):2495-2505
pubmed: 30345884
Cancer Discov. 2012 Apr;2(4):366-375
pubmed: 22576213
N Engl J Med. 2019 Dec 19;381(25):2391-2402
pubmed: 31562799
Nat Med. 2017 Apr;23(4):517-525
pubmed: 28288110