Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 14

1805P - Efficacy of olaparib (ola) + abiraterone (abi) vs placebo (pbo) + abi in the non-BRCA mutation (non-BRCAm) subgroup of patients (pts) with metastatic castration-resistant prostate cancer (mCPRC) in the PROpel trial

Date

21 Oct 2023

Session

Poster session 14

Topics

Clinical Research

Tumour Site

Prostate Cancer

Presenters

Niven Mehra

Citation

Annals of Oncology (2023) 34 (suppl_2): S954-S1000. 10.1016/S0923-7534(23)01946-4

Authors

N. Mehra1, N.W. Clarke2, A.J. Armstrong3, M. Oya4, N.D. Shore5, G. Procopio6, J.D.C. Guedes7, C. Arslan8, F. Parnis9, E. Brown10, F. Schlürmann11, J.Y. Joung12, M. Sugimoto13, Y.D. Choi14, D. Castellano15, Y. Urun16, C. Hosius17, C. Desai18, A. Degboe19, F. Saad20

Author affiliations

  • 1 Department Of Medical Oncology, Radboud Universitair Medisch Centrum, 6525 GA - Nijmegen/NL
  • 2 Department Of Urology, The Christie and Salford Royal NHS Foundation Trusts, Manchester/GB
  • 3 Department Of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, 27710 - Durham/US
  • 4 Department Of Urology, Keio University School of Medicine, 160-8582 - Tokyo/JP
  • 5 Department Of Uro-oncology, Carolina Urologic Research Center, 29572 - Myrtle Beach/US
  • 6 Department Of Oncology And Haematology, Istituto Nazionale Tumori Milano, 20133 - Milan/IT
  • 7 Department Of Clinical Oncology, Hospital de Base de São José do Rio Preto, 15090-000 - São José do Rio Preto/BR
  • 8 Department Of Oncology, Izmir Economy University Medical Park Hospital, 35575 - Karsiyaka/TR
  • 9 Department Of Oncology, Ashford Cancer Centre Research, 5035 - Kurralta Park/AU
  • 10 Department Of Oncology, University Hospital Southampton, SO16 6YD - Southampton/GB
  • 11 Department Of Oncology, Centre Hospitalier de Cornouaille, 29200 - Quimper/FR
  • 12 Department Of Urology, National Cancer Center, 10408 - Goyang-si/KR
  • 13 Department Of Urology, Kagawa University Hospital, 761-0793 - Kagawa/JP
  • 14 Department Of Urology, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 15 Department Of Medical Oncology, Hospital Universitario 12 de Octubre, 28041 - Madrid/ES
  • 16 Department Of Medical Oncology, Ankara University School of Medicine, 06590 - Ankara/TR
  • 17 Department Of Medical Affairs, MSD Sharp & Dohme GmbH, 85540 - Haar/DE
  • 18 Global Medicines Development, Oncology R&d, AstraZeneca, CB2 0AA - Cambridge/GB
  • 19 Global Medicines Development, Oncology R&d, AstraZeneca, 20878 - Gaithersburg/US
  • 20 Department Of Urology, Centre Hospitalier de l’Université de Montréal/CRCHUM, Université de Montreal, H2X 3J4 - Montreal/CA

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 1805P

Background

PROpel (NCT03732820) met its primary endpoint with a significant investigator-assessed radiographic progression-free survival (IA rPFS) benefit with ola + abi vs pbo + abi in the intention-to-treat (ITT) population in first-line mCRPC (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.001). At final pre-specified analysis there was a trend to improved overall survival (OS) with ola + abi vs pbo + abi (median 42.1 vs 34.7 months [m]; HR 0.81, 95% CI 0.67–1.00; P=0.0544). The greatest magnitude of benefits was seen in the BRCAm subgroup. Post hoc exploratory analyses were conducted to further investigate outcomes in non-BRCAm pts.

Methods

PROpel was a phase 3 double-blind trial. Pts were enrolled irrespective of biomarker status and randomized 1:1 to receive ola (300 mg twice daily [bid]) or pbo, and abi (1000 mg once daily) + prednisone/prednisolone (5 mg bid). Treatment continued until radiographic disease progression, unacceptable toxicity or withdrawal of consent. Aggregated tumour tissue (FoundationOne®CDx) and ctDNA (FoundationOne®Liquid CDx) test results, performed after randomization and before primary analysis, were used to classify pt mutation status. Non-BRCAm pts had no positive BRCAm test result and at least 1 negative BRCAm tissue or ctDNA result.

Results

In the non-BRCAm subgroup (n=693), there was a meaningful clinical benefit across endpoints for pts treated with ola + abi (Table). Safety profile of the combination was consistent with the ITT population. Within the non-BRCAm subgroup, analyses by baseline clinical characteristics showed consistent effect and will be presented. Table: 1805P

Non-BRCAm
Ola + abi (n=343) Pbo + abi (n=350) HR (95% CI)
Median (m):
IA rPFS* 24.1 19.0 0.76 (0.61–0.94)
BICR rPFS* 27.6 16.6 0.72 (0.58–0.90)
OS 39.6 38.0 0.91 (0.73–1.13)
Median time to (m):
PSA progression* 22.1 13.1 0.63 (0.50–0.79)
First subsequent therapy 24.0 19.9 0.84 (0.70–1.01)
First cytotoxic chemotherapy 30.1 22.7 0.80 (0.66–0.97)
Second progression or death NC NC 0.86 (0.65–1.14)
PSA 50 response,* % 78.6 71.4
ORR,* % 51.1 45.4
FACT-P change from baseline -6.3 -5.3
Any AE of CTCAE Grade ≥3, % 57.0 43.7
Any AE with outcome of death, % 7.0 4.9

*DCO1; 30/7/21 DCO3; 12/10/22 AE, adverse event; DCO, data cutoff; NC, not calculable; ORR, objective response rate; PSA, prostate-specific antigen

Conclusions

Exploratory analyses across multiple endpoints support a clinically meaningful benefit with ola + abi vs pbo + abi in non-BRCAm pts and a safety profile consistent with the overall ITT population.

Clinical trial identification

NCT03732820.

Editorial acknowledgement

Medical writing assistance was provided by Kirstin Spence, PhD, from Mudskipper Business Ltd, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, Roche, MSD, AstraZeneca, Astellas, JNJ; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Coordinating PI: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, co-PI: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-resistant Prostate Cancer Registry. N.W. Clarke: Financial Interests, Personal, Other, Honoraria: Janssen, AstraZeneca, Bayer; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Travel, accommodation, expenses: AstraZeneca. A.J. Armstrong: Financial Interests, Institutional, Advisory Role: Janssen, Novartis, Myovant Sciences, Bayer, Exelixis, Dendreon, Merck, GoodRx, AstraZeneca, FORMA Therapeutics, Astellas Scientific and Medical Affairs Inc, Pfizer, BMS; Financial Interests, Institutional, Research Funding: Gilead Sciences, Roche/Genentech, BMS, AstraZeneca, FORMA Therapeutics, Astellas Pharma, Constellation Pharmaceuticals, Dendreon, Pfizer, Amgen, Novartis, Janssen Oncology, Merck, Bayer, BeiGene; Financial Interests, Institutional, Royalties: Circulating tumor cell novel capture technology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas Scientific and Medical Affairs Inc.. M. Oya: Financial Interests, Personal, Other, Honoraria: Bayer, BMS, Novartis, Ono Pharmaceutical, Pfizer, AstraZeneca, Astellas, Takeda; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Research Funding: Novartis, Pfizer. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, PreView, Sanofi Genzyme, Speciality Networks, Sesen Bio, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Vaxiion, Asieris, Alessa Therapeutics, Akido, Arquer, Fize medical, GConcology, Genentech, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Profound, Promaxo, Protara, Vessi; Financial Interests, Personal, Member of Board of Directors: Photocure. G. Procopio: Financial Interests, Personal, Advisory Board, consultant fees: Astellas, AstraZeneca, Bayer, BMS, Janssen, Ipsen, Merck, MSD, Novartis, Pfizer; Financial Interests, Institutional, Research Grant, research funding for no profit clinical trial: Ipsen. J.D.C. Guedes: Financial Interests, Personal, Other, Honoraria: Merck, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Funding: Agenus, Amgen, AstraZeneca, Bayer, BMS, BRAVA, Daiichi Sankyo, Eurofarma, Genentech, HUYABIO, Incyte, Lilly, MSD, Pfizer, PTC, Roche, Sanofi, Takeda; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Gilead. C. Arslan: Financial Interests, Institutional, Invited Speaker: BMS, Bayer, Amgen, Teva, Lilly, Johnson &Johnson; Financial Interests, Institutional, Advisory Board: Novartis, Merck, AstraZeneca, Johnson &Johnson, Lilly, Astellas, Teva, BMS; Financial Interests, Institutional, Local PI: Roche, Novartis, BMS, Merck, AstraZeneca, Nektar, Johnson &Johnson, Lilly, Amgen, Bayer, Incyte. F. Parnis: Financial Interests, Personal, Invited Speaker: Bayer. F. Schlürmann: Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications, AstraZeneca, Astellas, Bayer; Financial Interests, Institutional, Advisory Role: Advanced Accelerator Applications, AstraZeneca, Astellas, Bayer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Advanced Accelerator Applications, AstraZeneca, Astellas, Bayer. M. Sugimoto: Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, Janssen, Takeda. D. Castellano: Financial Interests, Institutional, Advisory Role: Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, BMS, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, Boehringer Ingelheim; Financial Interests, Institutional, Research Funding: Janssen Oncology; Financial Interests, Personal, Other, Travel/accommodation support: Pfizer, Roche, BMS, AstraZeneca Spain. Y. Urun: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Janssen Oncology, Pfizer, BMS, Roche, MSD; Financial Interests, Personal, Invited Speaker: Astellas, Janssen Oncology, Pfizer, BMS, Roche, Amgen; Financial Interests, Personal and Institutional, Local PI: BMS, AstraZeneca, MSD, Janssen, Roche. C. Hosius: Financial Interests, Institutional, Full or part-time Employment: Merck Sharp & Dohme; Financial Interests, Personal, Stocks or ownership: Merck. C. Desai, A. Degboe: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Sanofi, Pfizer, Myovant, Novartis, AstraZeneca, Merck, Myovant; Financial Interests, Institutional, Local PI: Novartis, Astellas, Bayer, Janssen, Sanofi, BMS, Amgen, Pfizer, Merck; Financial Interests, Institutional, Coordinating PI: AstraZeneca. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.