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.

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 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.

RESULTS

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.

CONCLUSIONS

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.

Informations de copyright

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Déclaration de conflit d'intérêts

Declaration of Competing Interest The following authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Loverix Liselore: Personal financial interest: /. Support of Myriad testing and drug supply: AstraZeneca. Speakers fee to institution: AstraZeneca, GSK. Travel expenses: AstraZeneca, GSK, Twist Bioscience. Vergote Ignace: Consulting fees from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, Zentalis. Contracted research (via KULeuven) Oncoinvent AS. Corporate sponsored research: Amgen, Roche. Accommodations, travel expenses: Karyopharm, Genmab, Novocure. Vanderstichele Adriaan: Speaker’s bureau: Pfizer, GSK. Harter Philipp: Honoraria: Amgen, Astra Zeneca, GSK, Roche, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Mersana, Exscientia. Advisory Board: Astra Zeneca, Roche, GSK, Clovis, Immunogen, MSD, Novartis, Eisai. Research Funding (Inst): Astra Zeneca, Roche, GSK, Genmab, DFG, European Union, DKH, Immunogen, Seagen, Clovis, Novartis. Pignata Sandro: Honoraria and research funding from AstraZeneca, MSD, GSK, Roche, Pfizer. Baert Thais: Research grant: Roche. Travel/Conference support: GSK, MSD, astrazeneca. Consultancy fee: Tesaro/GSK. Speaker fee: Novartis. Gonzalez-Martin Antonio: ALKERMES, Advisory Board, Personal AMGEN, Advisory Board, Personal. ASTRA ZENECA, Advisory Board, Personal ASTRA ZENECA, Invited Speaker, Personal CLOVIS, Invited Speaker, Personal CLOVIS, Advisory Board, Personal Eisai, Advisory Board, Personal GENMAB, Advisory Board, Personal GSK, Invited Speaker, Personal. GSK, Advisory Board, Personal HederaDx, Advisory Board, Personal Illumina, Advisory Board, Personal Inmunogen, Advisory Board, Personal Macrogenics, Advisory Board, Personal MERSANA, Advisory Board, Personal MSD, Invited Speaker, Personal. MSD, Advisory Board, Personal. NOVARTIS, Advisory Board, Personal. NOVOCURE, Invited Speaker, Personal. ONCOINVENT, Advisory Board, Personal. PHARMAMAR, Advisory Board, Personal. Regeneron, Advisory Board, Personal. ROCHE, Advisory Board, Personal. ROCHE, Invited Speaker, Personal. SOTIO, Advisory Board, Personal. SUTRO, Advisory Board, Personal. Takeda, Invited Speaker, Personal. Zaylab, Invited Speaker, Personal. ARAVIVE, Coordinating PI, Institutional, No financial interest, ENGOT PI of AVB-500 phase III trial GSK, Coordinating PI, Institutional, No financial interest, PI of ANITA trial. MSD, Steering Committee Member, Personal, No financial interest, Member of ENGOT ov43-SC Novartis, Coordinating PI, Institutional, No financial interest, ENGOT PI of EPIK-O trial. Roche, Coordinating PI, Institutional, No financial interest, PI of ANITA trial. Marth Christian: Consulting fees: Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, Seagen. Honoraria for lectures, presentations,…: Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, Seagen. Support for attending meetings and/or travel: Roche, AstraZeneca. Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Novartis, Amgen, MSD, AstraZeneca, Pfizer, PharmaMar, GSK, Seagen. Neven Patrick: Personal financial interest: /. Institutional financial interest: AstraZeneca (Consultancy Ad Board, Steering Committee, Speakers Fee). Eli Lilly (Consultancy Ad Board, Steering Committee, Speakers Fee). Novartis (Consultancy Ad Board, Speakers Fee). Pfizer (Consultancy Ad Board, Speakers fee). Colombo Nicoletta: NC has reported fees for advisory board membership for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche; fees as an invited speaker for AstraZeneca, Novartis, Clovis Oncology, GSK, MSD/Merck; institutional research grants from AstraZeneca, and Roche. She has also reported non-remunerated activities as member of the ESMO Guidelines Steering Committee and chair of the Scientific Committee of ACTO (Alleanza contro il tumore ovarico). Mäenpää Johanna: Honoraria and research funding last 3 years: EISAI, MSD, AstraZeneca, GSK/Tesaro. Ray-Coquard Isabelle: Honoraria (self) from Agenus, Blueprint, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Macrogenics, Tesaro and Clovis; Honoraria (institution) from GSK, MSD, Roche and BMS; Advisory/consulting fees from Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; research grant/funding (self) from MSD, Roche and BMS; Research grant/funding (institution) from MSD, Roche, BMS, Novartis, Astra Zeneca and Merck Sereno; Travel support from Roche, MSD, AstraZeneca and GSK. Principal Investigator of PAOLA-1 trial. Pujade-Lauraine Eric: Advisory board: AstraZeneca GSK. Consultant: Roche. Data safety monitoring: Agenus, Incyte. Lambrechts Diether: Personal fees from Astra Zeneca (Advisory boards and speaker's fee), personal fees from MSD (Advisory boards), grants from Agilent Technologies (industry-sponsored grant). In addition, Dr. Lambrechts has a patent application pending. Van Gorp Toon: Consulting/advisory board: AstraZeneca, Eisai Europe, OncXerna therapeutics, MSD/Merck, GSK, ImmunoGen. Travel/accommodation/expenses: Amgen, Pfizer, Roche, Sanofi Aventis, Novartis, Immunogen, MSD, PharmaMar, GSK. Research funding: Amgen, Roche, AstraZeneca. Busschaert Pieter, Venken Tom, Boeckx Bram, Brems Hilde, Van Nieuwenhuysen Els, Han Sileny, Berteloot Patrick, Olbrecht Siel, Laga Tina, and Sablon Erwin have no conflict of interest.