TY - JOUR
T1 - Shallow whole genome sequencing approach to detect Homologous Recombination Deficiency in the PAOLA-1/ENGOT-OV25 phase-III trial
AU - Callens, Celine
AU - Rodrigues, Manuel
AU - Briaux, Adrien
AU - Frouin, Eleonore
AU - Eeckhoutte, Alexandre
AU - Pujade-Lauraine, Eric
AU - Renault, Victor
AU - Stoppa-Lyonnet, Dominique
AU - Bieche, Ivan
AU - Bataillon, Guillaume
AU - Karayan-Tapon, Lucie
AU - Rochelle, Tristan
AU - Heitz, Florian
AU - Cecere, Sabrina Chiara
AU - Pérez, Maria Jesús Rubio
AU - Grimm, Christoph
AU - Nøttrup, Trine Jakobi
AU - Colombo, Nicoletta
AU - Vergote, Ignace
AU - Yonemori, Kan
AU - Ray-Coquard, Isabelle
AU - Stern, Marc-Henri
AU - Popova, Tatiana
N1 - © 2023. The Author(s).
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - BRCA1 Protein/genetics
KW - BRCA2 Protein/genetics
KW - Female
KW - Homologous Recombination/genetics
KW - Humans
KW - Neoplasms
KW - Ovarian Neoplasms/diagnosis
UR - http://www.scopus.com/inward/record.url?scp=85175983536&partnerID=8YFLogxK
U2 - 10.1038/s41388-023-02839-8
DO - 10.1038/s41388-023-02839-8
M3 - Journal article
C2 - 37945748
SN - 0950-9232
VL - 42
SP - 3556
EP - 3563
JO - Oncogene
JF - Oncogene
IS - 48
ER -