BRCAAway: Abiraterone/olaparib shows survival gain in mCRPC

Frontline treatment with abiraterone acetate (Zytiga) plus olaparib (Lynparza) significantly improved progression-free (PFS) and overall survival (OS) compared with either agent alone in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 or ATM alterations, according to updated phase 2 BRCAAway trial (NCT03012321) results.¹

“BRCAAway is a biomarker preselected, randomized, open label, multicenter phase 2 trial which basically evaluated the efficacy of targeting the AR [androgen receptor] with abiraterone/prednisone vs olaparib vs combination in first-line metastatic castration-resistant patients who had germline and/or somatic HRR mutations in BRCA1, BRCA2, or ATM. The patients with other HRR mutations were treated with olaparib. That’s arm 4,” explained presenting author Maha Hussain, MD, FACP, FASCO, the Genevieve Teuton Professor of Medicine in the Division of Hematology-Oncology, Department of Medicine, and the deputy director, and leader of the GU Oncology Program at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine in Chicago, Illinois. Hussain presented the findings at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California.

Hussain noted that the trial was designed in 2016, which was before clinical trial results of AR pathway inhibitor and PARP inhibitor combination trials were available. Data from BRCAAway published in 2024 found that first-line treatment with abiraterone/olaparib was associated with significantly improved progression-free survival when compared with either agent alone or when the agents were used sequentially for patients with BRCA1/2 or ATM alterations.² For the study presented at ASCO GU 2026, Hussain reported on updated PFS and OS outcomes from BRCAAway.

Patients with mCRPC who had no prior exposure to a PARP inhibitor, AR pathway inhibitor, or chemotherapy were eligible for inclusion the study. Patients received tumor next-generation sequencing as well as germline testing. Patients in whom BRCA1/2 or ATM alterations were identified were randomly assigned 1:1:1 to arm 1 (abiraterone 100 mg once daily plus prednisone 5 mg twice daily), arm 2 (olaparib 300 mg twice daily), or arm 3 (olaparib plus abiraterone/prednisone). Patients who had other HRR mutations received olaparib 300 mg twice daily and switched to abiraterone/prednisone at disease progression. The primary end point was radiographic PFS per RECIST 1.1, Prostate Cancer Working Group 3, clinical assessment, or death. Secondary end points included measurable disease response rate, prostate-specific antigen response rate, and toxicity, as well as OS, which was defined as duration of time from date of treatment arm assignment to the time of death.

Hussain reported that 165 patients received somatic and germline testing, of whom 61 patients with BRCA1/2 or ATM alterations were randomly assigned to arms 1-3. In addition, 17 patients were assigned to arm 4.

“Interestingly, the combination arm had more patients with visceral disease, similarly with arm 4…and the majority of the patients who had the HRR mutations [had] BRCA2,” Hussain said.

Reporting on safety, Hussain said, “Overall, the treatment was very well tolerated. Essentially, there were very [few] grade 3 [adverse] events in both single-agent arms and in the combination arm. In arm 4, there was just 1 case of grade 3 and 1 case of grade 4.”

For arms 1 through 3, the objective response rate was 22%, 9.5%, and 33%, respectively. PSA responses rates in arms 1 through 3 were 61%, 67%, and 95%, respectively. Median PFS was 8.6 months (95% CI, 2.9-17) in arm 1, 14 months (95% CI, 8.4-20) in arm 2, and 39 months in arm 3 (95% CI, 22-NR). The HR for arm 3 vs arm 1 was 0.33 (95% CI, 0.15-0.72), and the HR for arm 3 vs arm 2 was 0.37 (95% CI, 0.17-0.84).

At disease progression, Hussain said 8 of 19 patients crossed over from abiraterone/prednisone to olaparib, and 8 of 21 patients crossed over from olaparib to abiraterone/prednisone. Median PFS for patients crossing over to olaparib was 8.3 months (95% CI, 5.5-15), and median PFS for patients crossing over to abiraterone/prednisone was 7.2 months (95% CI, 2.8-NR). Median PFS from randomization for patients crossing over to olaparib was 16 months (95% CI, 7.8-25) and median PFS from randomization for patients crossing over to abiraterone was 16 months (95% CI, 11-NR). The response rate to crossover treatment was 38% for patients crossing over to olaparib and 25% for patients crossing over to abiraterone. PSA response rate was 50% for patients crossing over to olaparib and 63% for patients crossing over to abiraterone. Hussain also reported a median PFS of 5 months (95% CI, 2-11) for arm 4.

Median OS was 28 months (95% CI, 13-NR) in arm 1, 37 months (95% CI, 26-NR) in arm 2, and 68 months (95% CI, 38-NR) in arm 3. Hussain described the arm 3 OS as “remarkable.” The HR for arm 1 vs 3 was 0.39 (95% CI, 0.16-.0.93), and the HR for arm 1 vs arm 2 was 0.51 (95% CI, 0.22-1.18). Median OS for arm 4 was 39 months (95% CI, 21-49).

“In patients with metastatic castration-resistant prostate cancer and BRCA1/2 or ATM alterations, abiraterone/prednisone plus olaparib was well tolerated and resulted in better response rates, progression-free survival, overall survival, and also PSA responses compared with olaparib or abiraterone despite allowing crossover. While the number of patients who crossed over was small, the frontline combination had a much better PFS, and the combination showed the longest survival,” Hussain said in her concluding remarks.

REFERENCES

1. Hussain M, Kocherginsky M, Paller CJ, et al. 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). Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract 16. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16923?presentation=256832

2. Hussain M, Kocherginsky M, Agarwal N, et al. Abiraterone, olaparib, or abiraterone + olaparib in first-line metastatic castration-resistant prostate cancer with DNA repair defects (BRCAAway). Clin Cancer Res. 2024;30(19):4318-4328. doi:10.1158/1078-0432.CCR-24-1402