Maha Hussain, MD, highlights phase 2 BRCAAway trial in mCRPC

In the following video, Maha H.A. Hussain, MD, FASCO, FACP, outlines the design and key findings from the phase 2 BRCAAway trial (NCT03012321), exploring the safety and efficacy of abiraterone (Zytiga) plus olaparib (Lynparza) vs each agent alone for the front-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with DNA repair defects. The results were presented at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California.¹

Hussain is a professor of medicine and oncology at Northwestern University as well as the Deputy Director for the Robert H Lori Comprehensive Cancer Center in Chicago, Illinois.

Hussain explained the rationale for the trial, which was motivated by emerging data suggesting that co-targeting AR and DNA repair pathways could yield meaningful clinical benefits. The core question driving the study was whether combination therapy offers advantages over sequential single-agent treatment, and, if sequential therapy proves equally effective, whether patients could be spared the burden of multiple simultaneous treatments.

The trial enrolled patients with frontline mCRPC who had not previously received an AR inhibitor, PARP inhibitor, or chemotherapy in that setting. Patients underwent both tissue and germline genomic testing; those with BRCA1, BRCA2, or ATM mutations were randomized 1:1:1 to abiraterone/prednisone (arm 1), olaparib (arm 2), or the combination (arm 3), with crossover permitted from the single-agent arms. Patients harboring other HRR mutations were enrolled in a separate arm (arm 4) receiving olaparib, with crossover to abiraterone allowed at progression. The primary end point was radiographic progression-free survival (rPFS), with secondary end points including prostate-specific antigen (PSA) response, measurable disease response, and toxicity.

Findings reported at this year's ASCO GU followed previously reported PFS benefits in 2024, which showed a median PFS of 39 months in the combination arm vs 14 months with olaparib alone (HR, 0.37; 95% CI, 0.17 to 0.84) and 8.6 months with abiraterone alone (HR, 0.33; 95% CI%, 0.15 to 0.72). At ASCO GU 2026, Hussain presented OS results from the study. Overall, the combination arm achieved a median overall survival exceeding 5 years (68 months), compared to 37 months for olaparib (HR, 0.51; 95% CI, 0.22 to 1.18) and 28 months for abiraterone alone (HR, 0.39; 95% CI, 0.16 to 0.93).

Notably, the safety profile was highly favorable, with no grade 4 or 5 toxicities observed in the primary treatment arms (arms 1 to 3). According to Hussain, grade 3 events were infrequent and largely consisted of manageable adverse effects such as fatigue and nausea, with no significant treatment discontinuations due to toxicity.

REFERENCE

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://www.asco.org/abstracts-presentations/256832/abstract