de-Bono, JohannMateo, JoaquinFizazi, KarimSaad, FredShore, NealSandhu, ShahneenChi, Kim NSartor, OliverAgarwal, NeerajOlmos, DavidThiery-Vuillemin, AntoineTwardowski, PrzemyslawMehra, NivenGoessl, CarstenKang, JinyuBurgents, JosephWu, WentingKohlmann, AlexanderAdelman, Carrie AHussain, Maha2023-02-082023-02-082020-04-28de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102http://hdl.handle.net/10668/15450Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in patients with prostate and other cancers. We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. Cohort A (245 patients) had at least one alteration in BRCA1, BRCA2, or ATM; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician's choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review. In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. 3.6 months; hazard ratio for progression or death, 0.34; 95% confidence interval, 0.25 to 0.47; P In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone.enPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProgression-Free SurvivalProstatic Neoplasms, Castration-ResistantAgedAged, 80 and overAndrostenesAntineoplastic AgentsAtaxia Telangiectasia Mutated ProteinsBenzamidesGenes, BRCA1Genes, BRCA2HumansLoss of Function MutationMaleMiddle AgedNeoplasm MetastasisNitrilesPhenylthiohydantoinresearch article32343890Restricted AccessGenesReparación del ADN por recombinaciónSupervivencia sin progresiónCastraciónProgresión de la enfermedadNeoplasias de la próstata10.1056/NEJMoa19114401533-4406https://doi.org/10.1056/nejmoa1911440