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.

May 29, 2023

Experts: Liselore Loverix,Ignace Vergote,Pieter Busschaert,Adriaan Vanderstichele,Tom Venken,Bram Boeckx,Philipp Harter,Hilde Brems,Els Van Nieuwenhuysen,Sandro Pignata,Thaïs 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

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.

Copyright © 2023 Elsevier Ltd. All rights reserved.

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ABOUT THE EXPERTS

Liselore Loverix,Ignace Vergote,Pieter Busschaert,Adriaan Vanderstichele,Tom Venken,Bram Boeckx,Philipp Harter,Hilde Brems,Els Van Nieuwenhuysen,Sandro Pignata,Thaïs 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

Liselore Loverix

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium; KU Leuven VIB Center for Cancer Biology, Lab of Translational Genetics, Leuven, Belgium.

Ignace Vergote

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Pieter Busschaert

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Adriaan Vanderstichele

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Tom Venken

KU Leuven VIB Center for Cancer Biology, Lab of Translational Genetics, Leuven, Belgium.

Bram Boeckx

KU Leuven VIB Center for Cancer Biology, Lab of Translational Genetics, Leuven, Belgium.

Philipp Harter

Department of Gynaecology & Gynaecologic Oncology, Ev. Kliniken Essen-Mitte, Essen, and Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), Germany.

Hilde Brems

University Hospitals Leuven, KU Leuven, Department of Human Genetics, Leuven, Belgium.

Els Van Nieuwenhuysen

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Sandro Pignata

Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, and Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO), Naples, Italy.

Thaïs Baert

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Antonio Gonzalez-Martin

Department of Medical Oncology, Clínica Universidad de Navarra, Program in Solid Tumors (CIMA), Pamplona, and Grupo Español de Investigación en Cáncer de Ovario (GEICO), Spain.

Sileny Han

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Christian Marth

Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, and AGO Austria, Austria.

Patrick Neven

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Nicoletta Colombo

University of Milan-Bicocca and European Institute of Oncology IRCCS, and Mario Negri Gynecologic Oncology Group (MANGO), Milan, Italy.

Patrick Berteloot

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Johanna Mäenpää

Department of Obstetrics and Gynecology and Cancer Center, Tampere University and University Hospital, Tampere, and Nordic Society of Gynecologic Oncology NSGO, Finland.

Siel Olbrecht

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Tina Laga

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium.

Erwin Sablon

KU Leuven VIB Center for Cancer Biology, Lab of Translational Genetics, Leuven, Belgium.

Isabelle Ray-Coquard

Department of Medical Oncology, Centre Léon Bérard University Claude Bernard, Lyon, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO), France.

Eric Pujade-Lauraine

Association de Recherche Cancers Gynécologiques (ARCAGY), Paris, France.

Diether Lambrechts

KU Leuven VIB Center for Cancer Biology, Lab of Translational Genetics, Leuven, Belgium.

Toon Van Gorp

University Hospitals Leuven, Leuven Cancer Institute (LKI), KU Leuven, and Belgium and Luxembourg Gynecologic Oncology Group (BGOG), Leuven, Belgium. Electronic address: toon.vangorp@uzleuven.be.