Dr Armstrong on the FDA Approval of Abiraterone/Olaparib Combination in BRCA-mutated mCRPC

Andrew J. Armstrong, MD, MSc, professor, medical oncology, surgery, pharmacology & cancer biology, Duke Cancer Center, member, Duke Cancer Institute, discusses the significance of the FDA approval of olaparib (Lynparza) plus abiraterone acetate (Zytiga) and prednisone or prednisolone in patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).

On May 31, 2023, the FDA approved olaparib plus abiraterone and prednisone or prednisolone in adult patients with mCRPC with deleterious or suspected deleterious BRCA mutations. This approval was based on findings from the phase 3 PROpel trial (NCT03732820), in which patients were randomized 1:1 to receive either olaparib plus abiraterone, and prednisone or prednisolone or placebo plus abiraterone, and prednisone or prednisolone. In the subgroup of patients in PROpel with BRCA-mutated mCRPC, the median radiographic progression-free survival (rPFS) was not reached in patients in the olaparib arm vs 8 months in those in the placebo arm, with a hazard ratio (HR) of 0.24

Patients with metastatic, hormone-resistant or castration-resistant prostate cancer have an unmet need for therapies that can delay disease progression and lead to improved survival, Armstrong says. In the frontline setting, these patients have traditionally received enzalutamide (Xtandi) or abiraterone, Armstrong notes. The PROpel trial was the first study to show a significant improvement in rPFS beyond standard-of-care abiraterone-based treatment, Armstrong emphasizes. The efficacy of the PARP inhibitor olaparib is meaningful for patients with BRCA-mutated mCRPC, who now have the PROpel regimen as an option to improve their rPFS and overall survival outcomes, Armstrong explains.

Common adverse effects in the olaparib arm included anemia, fatigue, nausea, diarrhea, decreased appetite, lymphopenia, dizziness, and abdominal pain, which were observed in 48%, 38%, 30%, 19%, 16%, 14%, and 13% of patients, respectively. Additionally, 18% of patients who received olaparib required 1 or more blood transfusions. Despite these risks, olaparib plus abiraterone and prednisone is an effective option in the first-line mCRPC setting, Armstrong concludes.