%0 Journal Article
%A de-Bono, Johann
%A Mateo, Joaquin
%A Fizazi, Karim
%A Saad, Fred
%A Shore, Neal
%A Sandhu, Shahneen
%A Chi, Kim N
%A Sartor, Oliver
%A Agarwal, Neeraj
%A Olmos, David
%A Thiery-Vuillemin, Antoine
%A Twardowski, Przemyslaw
%A Mehra, Niven
%A Goessl, Carsten
%A Kang, Jinyu
%A Burgents, Joseph
%A Wu, Wenting
%A Kohlmann, Alexander
%A Adelman, Carrie A
%A Hussain, Maha
%T Olaparib for Metastatic Castration-Resistant Prostate Cancer.
%D 2020
%U http://hdl.handle.net/10668/15450
%X Multiple 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. 
%K Phthalazines
%K Piperazines
%K Poly(ADP-ribose) Polymerase Inhibitors
%K Progression-Free Survival
%K Prostatic Neoplasms, Castration-Resistant
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