Scholars@Duke publication: Prostate-specific Antigen and Objective Response Analyses in PROpel: Olaparib Plus Abiraterone Versus Placebo Plus Abiraterone as First-line Therapy for Metastatic Castration-resistant Prostate Cancer.

Prostate-specific Antigen and Objective Response Analyses in PROpel: Olaparib Plus Abiraterone Versus Placebo Plus Abiraterone as First-line Therapy for Metastatic Castration-resistant Prostate Cancer.

Publication , Journal Article

Saad, F; Armstrong, AJ; Oya, M; Shore, N; Procopio, G; Guedes, JD; Arslan, C; Mehra, N; Brown, E; Joung, JY; Sugimoto, M; Sartor, O; Kang, J ...

Published in: Eur Urol Oncol

November 4, 2025

Published version (DOI) Link to item

BACKGROUND AND OBJECTIVE: PROpel (NCT03732820) demonstrated a statistically significant radiographic progression-free survival (rPFS) benefit with olaparib plus abiraterone (Ola + Abi) versus placebo plus abiraterone (P + Abi) in first-line metastatic castration-resistant prostate cancer (mCRPC). We conducted exploratory analyses in the intention-to-treat (ITT) population and subgroups stratified by homologous recombination repair gene mutation (HRRm) and BRCA1 and/or BRCA2 mutation (BRCAm) status. METHODS: In PROpel, patients with mCRPC, without selection by HRRm status, were randomised 1:1 to first-line treatment with Ola (300 mg twice daily; n = 399) or P (n = 397), each with Abi (1000 mg daily) and prednisone/prednisolone (5 mg twice daily). The primary endpoint was investigator-assessed rPFS. Exploratory endpoints were the objective response rate (ORR), duration of response (DoR), confirmed ≥50 decrease in prostate-specific antigen (PSA50-RR), and time to PSA progression; post hoc subgroup analyses by HRRm and BRCAm status were conducted. KEY FINDINGS AND LIMITATIONS: In the ITT population, the ORR was 58.4% with Ola + Abi versus 48.1% with P + Abi. The confirmed PSA50-RR was 79.3% with Ola + Abi and 69.2% with P + Abi. Median time to PSA progression in the ITT population was 24.2 mo with Ola + Abi and 12.0 mo with P + Abi (HR 0.59; 95% CI, 0.49-0.71). In the HRRm, no-HRRm, BRCAm, and no-BRCAm subgroups, results for ORR, DoR, confirmed PSA50-RR, and time to PSA progression favoured Ola + Abi, but these analyses were not powered for statistical significance. CONCLUSIONS AND CLINICAL IMPLICATIONS: Results for ORR, DoR, confirmed PSA50-RR, and time to PSA progression favoured Ola + Abi over P + Abi in the ITT population and biomarker subgroups. The data support consideration of Ola + Abi as first-line treatment for mCRPC.