BACKGROUND: We previously reported that olaparib led to significantly longer 
imaging-based progression-free survival than the physician's choice of 
enzalutamide or abiraterone among men with metastatic castration-resistant 
prostate cancer who had qualifying alterations in homologous recombination 
repair genes and whose disease had progressed during previous treatment with a 
next-generation hormonal agent. The results of the final analysis of overall 
survival have not yet been reported.
METHODS: In an open-label, phase 3 trial, we randomly assigned patients in a 2:1 
ratio to receive olaparib (256 patients) or the physician's choice of 
enzalutamide or abiraterone plus prednisone as the control therapy (131 
patients). Cohort A included 245 patients with at least one alteration in BRCA1, 
BRCA2, or ATM, and cohort B included 142 patients with at least one alteration 
in any of the other 12 prespecified genes. Crossover to olaparib was allowed 
after imaging-based disease progression for patients who met certain criteria. 
Overall survival in cohort A, a key secondary end point, was analyzed with the 
use of an alpha-controlled, stratified log-rank test at a data maturity of 
approximately 60%. The primary and other key secondary end points were reported 
previously.
RESULTS: The median duration of overall survival in cohort A was 19.1 months 
with olaparib and 14.7 months with control therapy (hazard ratio for death, 
0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the 
median duration of overall survival was 14.1 months with olaparib and 11.5 
months with control therapy. In the overall population (cohorts A and B), the 
corresponding durations were 17.3 months and 14.0 months. Overall, 86 of 131 
patients (66%) in the control group crossed over to receive olaparib (56 of 83 
patients [67%] in cohort A). A sensitivity analysis that adjusted for crossover 
to olaparib showed hazard ratios for death of 0.42 (95% CI, 0.19 to 0.91) in 
cohort A, 0.83 (95% CI, 0.11 to 5.98) in cohort B, and 0.55 (95% CI, 0.29 to 
1.06) in the overall population.
CONCLUSIONS: Among men with metastatic castration-resistant prostate cancer who 
had tumors with at least one alteration in BRCA1, BRCA2, or ATM and whose 
disease had progressed during previous treatment with a next-generation hormonal 
agent, those who were initially assigned to receive olaparib had a significantly 
longer duration of overall survival than those who were assigned to receive 
enzalutamide or abiraterone plus prednisone as the control therapy, despite 
substantial crossover from control therapy to olaparib. (Funded by AstraZeneca 
and Merck Sharp and Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).