We have previously reported that in men with metastatic castration-resistant prostate cancer, the homologous recombination repair gene has been appropriately changed and the disease has progressed during the previous treatment, so it is similar to the doctor’s choice of enzalutamide or abiraterone. Compared to, olaparib leads to a significantly longer imaging-based progression-free survival compared to next-generation hormones. The final analysis of the overall survival rate has not been reported.
In an open-label phase 3 trial, we randomly assigned patients to receive olaparib (256 patients) at a 2:1 ratio or the physician chose enzalutamide or abiraterone plus prednisone as the control therapy (131 patients). Cohort A includes at least 1 change in 245 patients BRCA1, BRCA2, Or ATM, Cohort B includes 142 patients, and at least one of the other 12 pre-designated genes has changed. For patients who meet certain criteria, they are allowed to switch to olaparib after imaging-based disease has progressed. The overall survival rate of cohort A (the key secondary endpoint) was analyzed by using alpha-controlled stratified log-rank test, and the data maturity was about 60%. The primary and other primary secondary endpoints have been reported previously.
The median overall survival time of cohort A was 19.1 months, compared with 14.7 months for control treatment (hazard ratio of death was 0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the median overall survival of the olaparib group was 14.1 months, and the control therapy was 11.5 months. In the total population (cohorts A and B), the corresponding durations were 17.3 months and 14.0 months, respectively. Overall, 86 of the 131 patients in the control group (66%) were cross-treated with olaparib (56 of 83 patients) [67%] In group A). The sensitivity analysis adjusted for crossover with olaparib showed that the risk ratio of death for cohort A was 0.42 (95% CI, 0.19 to 0.91), cohort B was 0.83 (95% CI, 0.11 to 5.98), and 0.55 (95% CI, total 0.29 to 1.06 in the population).
In men with metastatic castration-resistant prostate cancer, the tumor has at least one change BRCA1, BRCA2, Or ATM Moreover, in the case of previous next-generation hormone therapy, the disease has deteriorated, and the overall survival of patients who initially received olaparib was significantly longer than those who received enzalutamide or abiraterone plus prednisone as control treatments Patients, despite the substantial change from control therapy to olaparib. (Funded by AstraZeneca and Merck Sharp & Dohme; Profound ClinicalTrials.gov number, NCT02987543.)