FDA Approves Olaparib-Based Combination for BRCA-Mutated Metastatic Prostate Cancer

By: JNCCN 360 Staff
Posted: Friday, June 2, 2023

On May 31, the U.S. Food and Drug Administration (FDA) approved olaparib (Lynparza) plus abiraterone acetate (Zytiga) and prednisone (or prednisolone) for the treatment of adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer, as determined by an FDA-approved companion diagnostic test.

Efficacy was evaluated in the phase III PROpel trial of 796 patients with metastatic castration-resistant prostate cancer. Patients were randomly assigned (1:1) to receive either olaparib with abiraterone or placebo with abiraterone and received prednisone or prednisolone. A statistically significant improvement in radiologic progression–free survival with olaparib plus abiraterone compared with placebo plus abiraterone in the intent-to-treat population was observed.

An exploratory subgroup analysis in the 85 patients with BRCA-mutated disease (11% of the intent-to-treat population) demonstrated a median metastatic castration-resistant prostate cancer that was not reached with olaparib plus abiraterone compared with 8 months for those receiving placebo plus abiraterone (hazard ratio [HR] = 0.24). The overall survival hazard ratio in these patients was 0.30. In the 711 patients without BRCA-mutated disease, the radiologic progression–free survival hazard ratio was 0.77, and the overall survival hazard ratio was 0.92, suggesting the benefit in the intent-to-treat population was primarily attributable to patients with BRCA-mutated disease.

The most common adverse reactions (≥ 10%) in patients receiving olaparib plus abiraterone were anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%). A total of 72 patients (18%) required at least one blood transfusion, and 46 (12%) required multiple transfusions.

The recommended dose of olaparib is 300 mg taken orally twice daily with or without food. The recommended dose of abiraterone is 1,000 mg taken orally once daily. Abiraterone should be administered with prednisone or prednisolone at 5 mg orally twice daily. Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had a prior bilateral orchiectomy.

U.S. Food and Drug Administration

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