Publications
European Journal of CancerApr 2023 DOI:
10.1016/j.ejca.2023.04.020

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.

Liselore, Loverix; Ignace, Vergote; Pieter, Busschaert; Adriaan, Vanderstichele; Tom, Venken; Bram, Boeckx; Philipp, Harter; Hilde, Brems; Els, Van Nieuwenhuysen; Sandro, Pignata; Thais, Baert; Antonio, Gonzalez-Martin; Sileny, Han; Christian, Marth; Patrick, Neven; Nicoletta, Colombo; Patrick, Berteloot; Johanna, Mäenpää; Siel, Olbrecht; Tina, Laga; Erwin, Sablon; Isabelle, Ray-Coquard; Eric, Pujade-Lauraine; Diether, Lambrechts; Toon, Van Gorp
Product Used
Genes
Abstract
Background 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)). Patients and methods The academic Leuven HRD test consists of capture-based targeted sequencing of genome-wide SNPs and coding exons of 8 HR genes including BRCA1, BRCA2 and TP53. We compared the predictive value of the Leuven vs Myriad HRD tests for PFS and OS in the randomized PAOLA-1 trial. Results 468 patients had left-over DNA after Myriad testing for Leuven HRD testing. Positive/negative/overall percent agreement for the Leuven vs Myriad HRD status was 95%/86%/91%, respectively. Tumors were HRD+ in 55% and 52%, respectively. In Leuven HRD+ patients, 5 years PFS (5yPFS) was 48.6% vs 20.3% (HR 0.431; 95%CI0.312—0.595) for olaparib vs placebo, respectively (Myriad test 0.409; 95%CI0.292-0.572). In Leuven HRD+/BRCAwt patients 5yPFS was 41.3% vs 12.6% (HR 0.497; 95%CI0.316—0.783), and 43.6% vs 13.3% (HR 0.435; 95%CI0.261—0.727) for the Myriad test. 5yOS was prolonged in the HRD+ subgroup with both tests 67.2% vs 54.4% (HR 0.663; 95%CI0.442—0.995) for the Leuven test, and 68.0% vs 51.8% (HR 0.596 95%CI0.393—0.904) for the Myriad test. HRD status was undetermined in 10.7% and 9.4% of the samples, respectively. Conclusions A robust correlation between the Leuven HRD and Myriad test was observed. For HRD+ tumors, the academic Leuven HRD showed a similar difference in PFS and OS as the Myriad test.
Product Used
Genes

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