Overall survival from the phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in first-line metastatic castration-resistant prostate cancer (mCRPC) with DNA repair defects (BRCAAway).

16 Background: The BRCAAway trial evaluated the efficacy of abiraterone (Abi) versus olaparib (Ola) versus their combination as first-line therapy in patients (pts) with mCRPC harboring germline or somatic homologous recombination repair mutations (HRRm). It showed that first-line treatment with the Abi/Ola combination significantly improved progression-free survival (PFS) compared with either agent alone or sequentially in pts with BRCA1/2 or ATM alterations. Here, we report the overall survival (OS) outcomes per arm. Methods: BRCAAway was a multi-center, open-label, randomized, phase 2 trial. Eligible pts had progressive mCRPC with HRRm and no prior exposure to PARPi or Abi. Pts with HRRm in BRCA1/2 and/or ATM alterations were randomized 1:1:1 to Arm 1: abiraterone 1000 mg QD + prednisone 5 mg BID (Abi/pred), Arm 2: olaparib 300 mg BID (Ola), or Arm 3: abiraterone/prednisone + olaparib (Abi/pred + Ola). Pts with noncanonical HRRm received olaparib alone (nonrandomized Arm 4: exploratory). Crossover was permitted in Arms 1 and 2. OS was assessed as a key secondary endpoint. OS was measured from randomization until death, and pts were censored at their last clinical encounter. Median OS and landmark OS rates at 24, 36, and 60 months for each arm were estimated using the Kaplan-Meier method. Hazard ratios (HRs) between the randomized arms were obtained using Cox proportional hazards regression, separately comparing Arm 3 vs 1 and Arm 3 vs 2. Results: As of September 30, 2025 (data cutoff), there were 34/61 deaths in the randomized pts (11/19 Arm 1 pts, 13/21 Arm 2 pts, and 10/21 Arm 3 pts) and 12/17 deaths in exploratory Arm 4 pts. Median follow-up time was 46.2 months (m). Arm 3 had the longest median OS of 68 m (95% CI: 38–not reached NR), compared to Arm 1 median of 28 m (95% CI: 13–NR) and HR = 0.39 (95% CI: 0.16–0.93), and compared to Arm 2 median of 37 m (95% CI: 26–NR) and HR = 0.51 (95% CI: 0.22–1.18) (Table 1). Arm 3 also had the highest 24-, 36-, and 60-month landmark OS rates compared to Arms 1 and 2. Median OS for the exploratory Arm 4 was 39 m (95% CI: 21–49). Conclusions: In pts with mCRPC harboring BRCA1/2 or ATM alterations, abiraterone/prednisone + olaparib was well tolerated and resulted in significantly improved OS (median of >5 years) compared to either agent used alone or sequentially. Clinical trial information: NCT03012321 . Treatment Median OS (95% CI) in Months 24-Month OS Rate (95% CI) 36-Month OS Rate (95% CI) 60-Month OS Rate (95% CI) HR (95% CI) for Arm 3 vs Arm 1 and Arm 2 Arm 1: Abi/pred (n=19) 28 (13, NR) 55% (29%, 75%) 41% (18%, 63%) 31% (9.5%, 55%) 0.39 (0.16, 0.93) Arm 2: Ola (n=21) 37 (26, NR) 85% (60%, 95%) 53% (29%, 72%) 42% (21%, 63%) 0.51 (0.22, 1.18) Arm 3: Abi/pred + Ola (n=21) 68 (38, NR) 90% (67%, 98%) 86% (62%, 95%) 55% (30%, 74%) 1 reference Arm 4: Exploratory (n=17) 39 (21, 49) 66% (36%, 84%) 51% (24%, 73%) 15% (2.4%, 37%) -