Olaparib Plus Abiraterone and Prednisone Granted FDA Approval for BRCA-Mutated Prostate Cancer

On May 31, 2023, the US Food and Drug Administration (FDA) granted approval to olaparib plus abiraterone acetate and prednisone for the treatment of patients with metastatic castration-resistant prostate cancer with deleterious, or suspect deleterious, BRCA -mutations.

This approval was based on results from the phase 3 PROpel trial. This trial enrolled 796 patients with metastatic castration-resistant prostate cancer who had either undergone a prior orchiectomy or received gonadotropin-releasing hormone analogs, and who had not received prior systemic therapy for metastatic castration-resistant disease. Patients were randomized on a 1-to-1 basis to receive abiraterone acetate plus prednisone and either olaparib or placebo. All clinical samples were retrospectively tested for BRCA mutational status. The primary efficacy end point was radiological progression-free survival (rPFS) with overall survival (OS) as a secondary end point. 

There was a statistically significant improvement in rPFS seen in the treatment arm vs the placebo arm. In an exploratory subgroup of patients with BRCA mutations (n = 85; 11% of intent-to-treat population), those patients in the olaparib arm had a median rPFS that was not reached, compared to 8 months for those patients in the placebo arm (hazard ratio [HR]: 0.24; 95% confidence interval, 0.12 to 0.45). The OS HR for BRCA mutated patients was 0.30. Among the patients without BRCA mutations, the rPFS HR was 0.77 and the OS HR was 0.92, which suggests that the rPFS improvement seen in the total population can be largely attributed to improvement seen in patients with BRCA mutations. 

The most common adverse events seen in ≥10% of patients receiving olaparib were anemia, fatigue, nausea, diarrhea, decreased appetite, lymphopenia, dizziness, and abdominal pain. There were 72 patients (18%) who required at least 1 blood transfusion with 46 (12%) requiring multiple transfusions.

The recommended dose of olaparib is 300 mg taken twice daily. The recommended dose of abiraterone is 1000 mg taken once daily and should be administered with 5 mg of prednisone or prednisolone twice daily.

Source:

FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. US Food and Drug Administration. May 31, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-abiraterone-and-prednisone-or-prednisolone-brca-mutated-metastatic-castration