PARP inhibitor predictive value of the Leuven HRD test compared with Myriad MyChoice CDx PLUS HRD on 468 ovarian cancer patients from the PAOLA-1/ENGOT-ov25 trial

The PAOLA-1/ENGOT-ov25 trial showed improved progression-free (PFS) and overall survival (OS) in homologous recombination deficient (HRD) positive patients treated with olaparib, but not when HRD negative (HRD tested with MyChoice CDx PLUS [Myriad test]). The academic Leuven HRD test consists of cap...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:European journal of cancer (1990) 2023-07, Vol.188, p.131-139
Hauptverfasser: Loverix, Liselore, Vergote, Ignace, Busschaert, Pieter, Vanderstichele, Adriaan, Venken, Tom, Boeckx, Bram, Harter, Philipp, Brems, Hilde, Van Nieuwenhuysen, Els, Pignata, Sandro, Baert, Thaïs, Gonzalez-Martin, Antonio, Han, Sileny, Marth, Christian, Neven, Patrick, Colombo, Nicoletta, Berteloot, Patrick, Mäenpää, Johanna, Olbrecht, Siel, Laga, Tina, Sablon, Erwin, Ray-Coquard, Isabelle, Pujade-Lauraine, Eric, Lambrechts, Diether, Van Gorp, Toon
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The PAOLA-1/ENGOT-ov25 trial showed improved progression-free (PFS) and overall survival (OS) in homologous recombination deficient (HRD) positive patients treated with olaparib, but not when HRD negative (HRD tested with MyChoice CDx PLUS [Myriad test]). The academic Leuven HRD test consists of capture-based targeted sequencing of genome-wide single-nucleotide polymorphisms and coding exons of eight HR genes including BRCA1, BRCA2, and TP53. We compared the predictive value of the Leuven HRD versus Myriad HRD test for PFS and OS in the randomised PAOLA-1 trial. 468 patients had left-over DNA after Myriad testing for Leuven HRD testing. Positive/negative/overall percent agreement for the Leuven versus Myriad HRD status was 95%/86%/91%, respectively. Tumours were HRD+ in 55% and 52%, respectively. In Leuven HRD+ patients, 5years PFS (5yPFS) was 48.6% versus 20.3% (HR 0.431; 95% confidence intervals (CI) 0.312–0.595) for olaparib versus placebo, respectively (Myriad test 0.409; 95% CI 0.292–0.572). In Leuven HRD+/BRCAwt patients 5yPFS was 41.3% versus 12.6% (HR 0.497; 95% CI 0.316–0.783), and 43.6% versus 13.3% (HR 0.435; 95% CI 0.261–0.727) for the Myriad test. 5yOS was prolonged in the HRD+ subgroup with both tests 67.2% versus 54.4% (HR 0.663; 95% CI 0.442–0.995) for the Leuven test, and 68.0% versus 51.8% (HR 0.596 95% CI 0.393–0.904) for the Myriad test. HRD status was undetermined in 10.7% and 9.4% of the samples, respectively. A robust correlation between the Leuven HRD and Myriad test was observed. For HRD+ tumours, the academic Leuven HRD showed a similar difference in PFS and OS as the Myriad test. •Results of ENGOT HRD initiative on 468 shared FFPE samples of the PAOLA-1 trial.•Academic Leuven HRD test shows comparable results with Myriad MyChoice HRD test.•Leuven HRD test confirms the impact of olaparib on PFS and OS in the HRD+ patients.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2023.04.020