RT Journal Article
T1 Olaparib for Metastatic Castration-Resistant Prostate Cancer.
A1 de-Bono, Johann
A1 Mateo, Joaquin
A1 Fizazi, Karim
A1 Saad, Fred
A1 Shore, Neal
A1 Sandhu, Shahneen
A1 Chi, Kim N
A1 Sartor, Oliver
A1 Agarwal, Neeraj
A1 Olmos, David
A1 Thiery-Vuillemin, Antoine
A1 Twardowski, Przemyslaw
A1 Mehra, Niven
A1 Goessl, Carsten
A1 Kang, Jinyu
A1 Burgents, Joseph
A1 Wu, Wenting
A1 Kohlmann, Alexander
A1 Adelman, Carrie A
A1 Hussain, Maha
K1 Phthalazines
K1 Piperazines
K1 Poly(ADP-ribose) Polymerase Inhibitors
K1 Progression-Free Survival
K1 Prostatic Neoplasms, Castration-Resistant
AB 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. 
PB Massachusetts Medical Society
YR 2020
FD 2020-04-28
LK http://hdl.handle.net/10668/15450
UL http://hdl.handle.net/10668/15450
LA en
NO de 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):2091-2102
DS RISalud
RD Apr 8, 2025