(UroToday.com) The 2026 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Maha Hussain discussing overall survival from the BRCAAway phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in first-line mCRPC with DNA repair defects. The BRCAAway trial evaluated the efficacy of abiraterone versus olaparib versus their combination as first-line therapy in patients with mCRPC harboring germline or somatic homologous recombination repair (HRR) mutations. It showed that first line treatment with the abiraterone + olaparib combination significantly improved progression free survival compared with either agent alone or sequentially in patients with BRCA1/2 or ATM alterations.1 At ASCO GU 2026, Dr. Hussain and colleagues reported the overall survival outcomes per arm.
BRCAAway was a multi-center, open-label, randomized, phase 2 trial. Eligible patients had progressive mCRPC with HRR mutations and no prior exposure to PARP inhibitors or abiraterone. Patients with HRR mutations in BRCA1/2 and/or ATM alterations were randomized 1:1:1 to:
- Arm 1: abiraterone 1000 mg QD + prednisone 5 mg BID (abiraterone + prednisone)
- Arm 2: olaparib 300 mg BID (olaparib)
- Arm 3: abiraterone/prednisone + olaparib (abiraterone + prednisone + olaparib)
Patients with noncanonical HRR mutations received olaparib alone (nonrandomized Arm 4: exploratory)
Crossover was permitted in Arms 1 and 2. Overall survival was assessed as a key secondary endpoint. Overall survival was measured from randomization until death, and patients were censored at their last clinical encounter. The median overall survival and landmark overall survival rates at 24, 36, and 60 months for each arm were estimated using the Kaplan-Meier method. Hazard ratios between the randomized arms were obtained using Cox proportional hazards regression, separately comparing Arm 3 versus Arm 1 and Arm 3 versus Arm 2.
There were 165 eligible patients registered from 15 sites who underwent somatic and germline testing. Overall, 61 patients with a qualifying alteration were randomized to Arms 1-3, with the following baseline characteristics:
Treatment related adverse events by arm were most commonly anemia, fatigue, and nausea:
The combination of abiraterone + prednisone + olaparib had the highest objective response rate (33%) and PSA response rate (95%):
With regards to progression free survival, the HR for abiraterone + prednisone + olaparib versus abiraterone + prednisone was 0.33 (95% CI 0.15-0.72) and for abiraterone + prednisone + olaparib versus olaparib was 0.37 (95% CI 0.17-0.84):
The progression free survival swimmer plots are as follows:
In the exploratory arm 4 (n = 17), the median progression free survival was 5 months (95% CI 2-11), with the following swimmer plot:
As of September 30, 2025 (data cutoff), there were 34/61 deaths in the randomized patients (11/19 Arm 1 patients, 13/21 Arm 2 patients, and 10/21 Arm 3 patients) and 12/17 deaths in exploratory Arm 4 patients. Over a median follow-up of 46.2 months, Arm 3 had the longest median overall survival of 68 months (95% CI: 38–not reached), compared to Arm 1 median of 28 months (95% CI: 13– not reached), with a HR of 0.39 (95% CI 0.16–0.93), and compared to Arm 2 median of 37 months (95% CI 26– not reached), with a HR of 0.51 (95% CI 0.22–1.18):
Arm 3 also had the highest 24-, 36-, and 60-month landmark overall survival rates compared to Arms 1 and 2. The median overall survival for the exploratory Arm 4 was 39 months (95% CI 21–49):
A summary of the overall survival findings is highlighted in the following table:
Dr. Hussain concluded her presentation discussing overall survival from the BRCAAway phase 2 trial with the following take-home points:
- In patients with mCRPC and BRCA1/2 or ATM alterations, abiraterone + prednisone + olaparib was well tolerated and resulted in better response rates, progression free survival, and overall survival versus olaparib or abiraterone + prednisone or cross over
- While the number of patients who crossed over was small, the front line combination had better progression free survival compared to sequential therapy
- Abiraterone + prednisone + olaparib showed the longest survival (median > 5 years) compared to either agent alone or sequentially
- On May 31, 2023, the FDA approved the combination of abiraterone + prednisone + olaparib as a front-line therapy for patients with mCRPC and BRCA1/2 DDR alterations
- In 2023, the FDA also approved niraparib + abiraterone + prednisone, as well as talazoparib + enzalutamide
Presented by: Maha Hussain, MD, Northwestern University, Chicago, IL
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 26 – Sat, Feb 28, 2026.
Related content: BRCAAway Trial Investigates Combination Versus Sequencing of ARPI and PARP Inhibitor in mCRPC - Maha Hussain
References: