Efficacy of Olaparib Plus Abiraterone for Patients with Metastatic Castration-resistant Prostate Cancer and Single Homologous Recombination Repair Gene Mutations in PROpel.

Abstract

PROpel (phase 3 randomized [1:1], double-blind trial: NCT03732820) met its primary endpoint, showing statistically significantly improved investigator-assessed radiographic progression-free survival (rPFS) with olaparib plus abiraterone versus placebo plus abiraterone in biomarker-unselected first-line metastatic castration-resistant prostate cancer (mCRPC; hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.54-0.81; p < 0.0001). Median overall survival (OS) was 42.1 mo with olaparib plus abiraterone, a 7.4-mo improvement versus placebo plus abiraterone. We report efficacy in patients with single homologous recombination repair gene mutations (HRRm). Before primary analysis, HRRm status was determined by aggregating tumor tissue (FoundationOne CDx) and circulating tumor DNA (FoundationOne Liquid CDx) assay results. Overall, 28.4% of patients had an HRRm, predominantly BRCA2 (7.3%), ATM (6.2%), and CDK12 (5.0%). HRs numerically favored olaparib plus abiraterone for rPFS (BRCA2, HR, 0.20; 95% CI, 0.08-0.44; ATM, HR, 0.55; 95% CI, 0.20-1.38; CDK12, HR, 0.51; 95% CI, 0.20-1.18) and OS (BRCA2, HR, 0.20; 95% CI, 0.07-0.48; ATM, HR, 0.79; 95% CI, 0.33-1.77; CDK12, HR, 0.57; 95% CI, 0.24-1.27). Other single-gene mutations were rare (<5 events in either arm), limiting interpretation. Findings support olaparib plus abiraterone as an important first-line option for patients with mCRPC. PREVIOUS PRESENTATION: Results were previously presented in part at the ASCO-GU 2024 congress, held on January 25-27, 2024: San Francisco, CA, USA.