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Christinat, Y; Labidi-Galy, I; Ho, L; Clément, S; Genestie, C; Sehouli, J; Cinieri, S; Gonzalez-Martin, A; Kolovetsiou-Kreiner, V; Fujiwara, K; Von, Gorp, T; Tognon, G; Hietanen, S; Heinzelmann-Schwarz, V; Ray-Coquard, I; Pujade-Lauraine, E; McKee, TA.
Geneva Homologous Recombination Deficiency Test Is Predictive of Survival Benefit From Olaparib and Bevacizumab Maintenance in Ovarian Cancer.
JCO Precis Oncol. 2025; 9:e2400825 Doi: 10.1200/PO-24-00825 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Kolovetsiou-Kreiner Vassiliki
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Abstract:: PURPOSE: The ability of the Geneva homologous recombination deficiency (HRD) test to predict progression-free survival (PFS) in patients with high-grade ovarian cancer treated with poly (ADP-ribose) polymerase inhibitors has been demonstrated. Its performance with respect to overall survival (OS) has not been assessed yet. METHODS: Using the final results of the PAOLA-1/ENGOT-ov25 phase III clinical trial with a median follow-up of 5 years, we evaluated the Geneva HRD test on 468 samples as part of the ENGOT HRD European Initiative. Results were evaluated in terms of final PFS and OS in the olaparib + bevacizumab and placebo + bevacizumab arms and compared with the Myriad MyChoice HRD test. RESULTS: Final PFS was consistent with previously published data and confirmed the predictive value of the Geneva HRD test with a hazard ratio (HR) of 0.41 (95% CI, 0.30 to 0.57) for HRD-positive patients. The results for OS showed a HR of 0.56 (95% CI, 0.37 to 0.85) for HRD-positive patients and 1.6 (95% CI, 1.1 to 2.3) for HRD-negative patients. These results are consistent with those observed with the Myriad test, including the negative OS trend in the HRD-negative subgroup treated with olaparib + bevacizumab (HR, 1.2 [95% CI, 0.83 to 1.8]). A subgroup analysis of patients with intermediate HRD scores showed that the normalized large-scale state transition score used by the Geneva HRD test had both predictive and prognostic value. CONCLUSION: The Geneva HRD test predicts PFS and OS benefit from olaparib + bevacizumab. The potential detrimental effect of olaparib + bevacizumab on OS in the HRD-negative population is hypothesis-generating and needs to be confirmed prospectively.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Female - administration & dosage; Bevacizumab - therapeutic use, administration & dosage; Phthalazines - therapeutic use, administration & dosage; Ovarian Neoplasms - drug therapy, genetics, mortality; Piperazines - therapeutic use, administration & dosage; Middle Aged - administration & dosage; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Homologous Recombination - administration & dosage; Aged - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Progression-Free Survival - administration & dosage; Adult - administration & dosage; Predictive Value of Tests - administration & dosage