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

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...

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Detalles Bibliográficos
Autores principales: Callens, Celine, Rodrigues, Manuel, Briaux, Adrien, Frouin, Eleonore, Eeckhoutte, Alexandre, Pujade-Lauraine, Eric, Renault, Victor, Stoppa-Lyonnet, Dominique, Bieche, Ivan, Bataillon, Guillaume, Karayan-Tapon, Lucie, Rochelle, Tristan, Heitz, Florian, Cecere, Sabrina Chiara, Pérez, Maria Jesús Rubio, Grimm, Christoph, Nøttrup, Trine Jakobi, Colombo, Nicoletta, Vergote, Ignace, Yonemori, Kan, Ray-Coquard, Isabelle, Stern, Marc-Henri, Popova, Tatiana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673712/
https://www.ncbi.nlm.nih.gov/pubmed/37945748
http://dx.doi.org/10.1038/s41388-023-02839-8
Descripción
Sumario: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.