dc.contributor
Institut Català de la Salut
dc.contributor
[Mateo J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [de Bono JS] The Institute of Cancer Research and Royal Marsden, London, United Kingdom. [Fizazi K] Institut Gustave Roussy, University of Paris Saclay, Villejuif, France. [Saad F] Centre de recherche du Centre Hospitalier de l’Université de Montréal/ CRCHUM, Universite de Montréal, Montréal, QC, Canada. [Shore N] Carolina Urologic Research Center, Myrtle Beach, SC. [Sandhu S] Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Fizazi, Karim
dc.contributor.author
Saad, Fred
dc.contributor.author
de Bono, Johann S
dc.contributor.author
Shore, Neal
dc.contributor.author
Sandhu, Shahneen
dc.contributor.author
Mateo, Joaquin
dc.date.accessioned
2025-10-25T05:37:59Z
dc.date.available
2025-10-25T05:37:59Z
dc.date.issued
2024-02-13T12:35:05Z
dc.date.issued
2024-02-13T12:35:05Z
dc.date.issued
2024-02-10
dc.identifier
Mateo J, de Bono JS, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial. J Clin Oncol. 2024 Feb 10;42(5):571–83.
dc.identifier
https://hdl.handle.net/11351/11037
dc.identifier
10.1200/JCO.23.00339
dc.identifier.uri
http://hdl.handle.net/11351/11037
dc.description.abstract
Olaparib; Castration-resistant prostate cancer
dc.description.abstract
Olaparib; Cáncer de próstata resistente a la castración
dc.description.abstract
Olaparib; Càncer de pròstata resistent a la castració
dc.description.abstract
Purpose
Phase III PROfound trial (ClinicalTrials.gov identifier: NCT02987543) met its primary and key secondary objectives, demonstrating significantly longer radiographic progression-free survival (rPFS) and overall survival (OS) with olaparib monotherapy versus abiraterone or enzalutamide (control) in patients with metastatic castration-resistant prostate cancer (mCRPC) with alterations in BRCA1, BRCA2 (BRCA), and/or ATM (cohort A) whose disease had progressed on prior next-generation hormonal agent (NHA). We report exploratory post hoc analysis of the subgroup of patients with mCRPC with BRCA alterations in PROfound.
Methods
All patients had an alteration in a homologous recombination repair gene by tumor tissue testing, of which 160 had underlying BRCA alterations. rPFS and OS were estimated using the Kaplan-Meier method. Confirmed objective response rate and safety were also assessed.
Results
Olaparib was associated with longer rPFS (hazard ratio [HR], 0.22 [95% CI, 0.15 to 0.32]) and OS (HR, 0.63 [95% CI, 0.42 to 0.95]) than control. There was an rPFS benefit with olaparib in all zygosity subgroups (biallelic [n = 88]; HR, 0.08 [95% CI, 0.04 to 0.16], heterozygous [n = 15] and unknown [n = 57]; HR, 0.30 [95% CI, 0.16 to 0.60]). Patients with BRCA2 homozygous deletions experienced prolonged responses to olaparib (n = 16; median rPFS, 16.6 months [95% CI, 9.3 to not reached]). Some evaluations are limited by small patient numbers. Germline DNA analysis was performed for 112 (70%) patients; risk of disease progression was similar for patients with germline (n = 61; HR, 0.08 [95% CI, 0.03 to 0.18]) and somatic (n = 51; HR, 0.16 [95% CI, 0.07 to 0.37]) BRCA alterations.
Conclusion
In all subgroups assessed, olaparib improved outcomes versus abiraterone or enzalutamide for patients with mCRPC with BRCA alterations whose disease had progressed on previous NHA.
dc.description.abstract
Supported by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ.
dc.format
application/pdf
dc.publisher
American Society of Clinical Oncology
dc.relation
Journal of Clinical Oncology;42(5)
dc.relation
https://doi.org/10.1200/JCO.23.00339
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Medicaments antineoplàstics - Ús terapèutic
dc.subject
Pròstata - Càncer - Tractament
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Anomalies cromosòmiques
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DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant
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Other subheadings::Other subheadings::Other subheadings::/drug therapy
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PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
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CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración
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Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
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FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
dc.title
Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
