PROfound Phase III trial results

According to the World Cancer Research Fund, prostate cancer is the second most commonly occurring cancer in men and the fourth most cancer overall. Approximately 10—20% of men with advanced prostate cancer will develop CRPC in five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis. Even with advancements in the treatment of men with mCRPC, five-year survival is low, and extending survival remains a key treatment goal.

PROfound is an open-label phase III trial where patients are randomly assigned in a 2:1 ratio to take olaparib (256 patients) or the doctor’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 endpoint, 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 endpoints were reported previously.


Results of the phase III trial of Lynparza (olaparib) established a clinically meaningful improvement as 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 the 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.

These exceptional results established by Lynparza across key endpoints in PROfound and the final overall survival results strengthen its potential to change the treatment standard for men with metastatic castration-resistant prostate cancer. The PROfound trial displays that Lynparza can play an important role in this new era of precision medicine in prostate cancer, and it will transform the treatment landscape for certain men with mCRPC. Also, Lynparza is the only PARP inhibitor to establish overall survival versus enzalutamide or abiraterone for men with BRCA or ATM mutations.

Also, as per Delveinsight report titled “Prostate Cancer - Market Insights, Epidemiology, and Market Forecast-2030Lynparza (olaparib) has already shown better efficacy compared to abiraterone or enzalutamide and hence expected to garner the maximum sales. It is also expected to dominate the market in the future with a significant market share.