The PROfound clinical trial showed that patients with metastatic castration-resistant prostate cancer (mCRPC) who harbored homologous recombination repair gene mutations (HRRm) benefited from receiving olaparib monotherapy. This is the first real-world study in the U.S. to evaluate olaparib monotherapy in patients with mCRPC and HRRm.
This retrospective study used data abstracted from electronic medical records in the ConcertAI Oncology Dataset. Patients with confirmed mCRPC, diagnosed between 2012 and 2023, age ≥21 years, treated with olaparib monotherapy (post-May 19, 2020) after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. HRR genes of interest were ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L. Biomarker testing patterns and treatment patterns were reported from initial prostate cancer diagnosis. Kaplan-Meier analysis was used to estimate real-world time on treatment (rwToT), progression-free survival (rwPFS), and overall survival (rwOS) from the earliest olaparib monotherapy exposure (index date). Patients were stratified by mutation status (any BRCA mutation and non-BRCA HRRm) and receipt of chemotherapy before index.
Overall, 144 patients were included in the study, with 74 patients (51.4%) having any BRCAm (including co-occurring mutations) and 70 (48.6%) having non-BRCA HRRm. Overall, the median age was 73 years, and 73.6% were White. Nearly 60% of patients received olaparib monotherapy in 4L or greater from initial prostate cancer diagnosis. Over half received at least 1 regimen of chemotherapy before index. Overall, the median rwPFS was 4.5 months (6.7 months for patients with any BRCAm and 3.4 months for patients with non-BRCA HRRm). Overall, the median rwOS was 16.5 months (20.3 months for patients with any BRCAm and 12.9 months for non-BRCA HRRm).
Earlier biomarker testing and retesting should be considered to improve outcomes with targeted therapy.
This study evaluated 144 patients with metastatic castration-resistant prostate cancer (mCRPC) who harbored homologous recombination repair gene mutations (HRRm) and treated with olaparib monotherapy after exposure to abiraterone or enzalutamide. Earlier biomarker testing and retesting for previously unrecognized or newly acquired mutations should be considered for patients with mCRPC. Patients may benefit from improved outcomes with targeted therapy when appropriate.
Urologic oncology. 2026 Jul 10 [Epub ahead of print]
Daniel J George, Furaha Kariburyo-Yay, Himani Aggarwal, Jon G Tepsick, Rebekah Yu, Weiyan Li, Chinelo Orji, Sameer R Ghate
Duke University, Durham, NC. Electronic address: ., ConcertAI, LLC, Cambridge, MA., Merck & Co., Inc., Rahway, NJ., AstraZeneca, Wilmington, DE.