Efficacy of Olaparib Plus Abiraterone for Patients with Metastatic Castration-resistant Prostate Cancer and Single Homologous Recombination Repair Gene Mutations in PROpel
In brief
Olaparib plus abiraterone cuts progression risk by 80% in BRCA2-mutated prostate cancer
In the PROpel trial, patients with metastatic castration-resistant prostate cancer harboring a single BRCA2 repair gene mutation experienced an 80% lower risk of radiographic progression when treated with olaparib plus abiraterone versus abiraterone alone. Similar trends were seen for ATM and CDK12 mutations, though numbers were smaller. These results suggest a strong first-line option for BRCA2-mutated mCRPC, pending confirmation in larger mutation-specific cohorts.
- Journal
- European urology oncology (Q1)
- Published
- 13 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Neal Shore, Noel W Clarke, Andrew J Armstrong, Mototsugu Oya, Giuseppe Procopio, João Daniel Guedes, et al.
- PMID
- 42595654
- DOI
- 10.1016/j.euo.2026.07.014
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 16 August 2026): Phase III RCT, olaparib + abiraterone improves OS
- Picked for Urology (top studies of the week, 16 August 2026): Phase III RCT, olaparib plus abiraterone in mCRPC
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.