BRCAAway - a Randomized Phase 2 Trial of Abiraterone, Olaparib, or Abiraterone + Olaparib in Patients with mCRPC with DNA Repair Defects - Maha Hussain

August 2, 2022

Maha Hussain is discussing the BRCAAway with Alicia Morgans, based upon Dr Hussain's presentation at ASCO 2022.  The BRCAAway Trial is a randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with mCRPC with DNA repair defects either in the tumor or germline. The PARP-inhibitor olaparib is approved for mCRPC patients with deleterious germline or somatic homologous recombination repair gene mutations. PARP1 interacts with androgen signaling, and castration-resistant tumor cells exhibit increased PARP1 activity. Preclinically, PARP1-inhibition synergizes with androgen receptor targeted therapy. BRCAAway is a biomarker selected, randomized, open-label, multicenter phase 2 trial evaluating the efficacy of targeting androgen receptor vs PARP vs combination in first-line mCRPC patients with germline and/or somatic homologous recombination repair gene mutations in BRCA1, BRCA2, or ATM.  Eligible mCRPC pts underwent tumor next-generation sequencing and germline testing. Pts with inactivating BRCA1, BRCA2 and/or ATM alterations were randomized 1:1:1 to Arm 1 abiraterone (1000 mg daily) + prednisone (5mg bid) (Abi/pred), Arm 2 olaparib (300 mg bid) or Arm 3 olaparib + Abi/pred. The primary endpoint is progression-free survival (PFS) analyzed using Kaplan-Meier estimates and Cox regression. Secondary endpoints include measurable disease response rate (RR) by RECIST, PSA-RR, undetectable PSA (≤ 0.2 ng/ml), and toxicity. Arms 1 and 2 pts were allowed to cross over at progression.

Dr. Hussain concluded by discussing the randomized phase 2 BRCAAway by emphasizing that in mCRPC patients with inactivating BRCA1, BRCA2, and/or ATM alterations, abiraterone + prednisone + olaparib was well tolerated and resulted in longer PFS and better PSA response versus either agent alone.

Biographies:

Maha Hussain, MD, FACP, FASCO, is the Genevieve Teuton Professor of Medicine in the Division of Hematology-Oncology, Department of Medicine, and the Deputy Director at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

ASCO 2022: Discussant: AR and PARP: Partners in Crime
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