Olaparib for Metastatic Castration-Resistant Prostate Cancer.
The New England journal of medicine
BACKGROUND: 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.
METHODS: 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
RESULTS: 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
CONCLUSIONS: 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. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).
de Bono, Johann; Mateo, Joaquin; Fizazi, Karim; Saad, Fred; Shore, Neal; Sandhu, Shahneen; Chi, Kim N; Sartor, Oliver; Agarwal, Neeraj; Olmos, David; Thiery-Vuillemin, Antoine; Twardowski, Przemyslaw; Mehra, Niven; Goessl, Carsten; Kang, Jinyu; Burgents, Joseph; Wu, Wenting; Kohlmann, Alexander; Adelman, Carrie A; and Hussain, Maha, "Olaparib for Metastatic Castration-Resistant Prostate Cancer." (2020). Articles, Abstracts, and Reports. 3095.