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

Oncogene. 2023 Nov;42(48):3556-3563. doi: 10.1038/s41388-023-02839-8. Epub 2023 Nov 9.


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.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Female
  • Homologous Recombination / genetics
  • Humans
  • Neoplasms*
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics


  • BRCA1 protein, human
  • BRCA1 Protein
  • BRCA2 protein, human
  • BRCA2 Protein