European urology oncology
August 13, 2026 · via Europe PMC
Efficacy of Olaparib Plus Abiraterone for Patients with Metastatic Castration-resistant Prostate Cancer and Single Homologous Recombination Repair Gene Mutations in PROpel.
Shore N, Clarke NW, Armstrong AJ, +15 more, Saad F.
AI summary — for doctors, generated from the abstract only
In PROpel subgroup analyses, olaparib plus abiraterone showed the strongest benefit in BRCA2-mutated mCRPC (rPFS and OS HR 0.20), with numerically favorable but imprecise effects for ATM and CDK12.
What was studied
Subgroup analysis of the phase 3 double-blind PROpel trial (NCT03732820) of first-line olaparib plus abiraterone vs placebo plus abiraterone in mCRPC, reporting efficacy by single HRR gene mutation determined by tissue and ctDNA assays.
Key findings
- 28.4% had an HRR mutation: BRCA2 7.3%, ATM 6.2%, CDK12 5.0%
- BRCA2: rPFS HR 0.20; OS HR 0.20
- ATM: rPFS HR 0.55; OS HR 0.79 (CIs crossing 1)
- CDK12: rPFS HR 0.51; OS HR 0.57 (CIs crossing 1)
- Other single-gene mutations too rare to interpret
Clinical relevance
This supports olaparib plus abiraterone particularly for BRCA2-mutated mCRPC, while effects in ATM and CDK12 subgroups remain uncertain due to small numbers.
Who should care
Limitations
Subgroup analyses with small numbers and wide confidence intervals; not powered for individual genes.
BRCA2-mutated mCRPC patients gain most from adding olaparib to abiraterone; benefit for other HRR genes is less certain.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
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.
DOI
10.1016/j.euo.2026.07.014
PMID
42595654
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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