FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer

On May 31, 2023, the Food and Drug Administration approved olaparib (Lynparza, AstraZeneca Pharmaceuticals LP) with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.

View full prescribing information for Lynparza.

Efficacy was evaluated in the PROpel trial (NCT03732820) that enrolled 796 patients with mCRPC, Patients were randomized (1:1) to receive either olaparib with abiraterone or placebo with abiraterone and also received prednisone or prednisolone. Patients were required to have a prior orchiectomy and, if not performed, received gonadotropin-releasing hormone (GnRH) analogs. Patients with prior systemic therapy for mCRPC were excluded; however, prior docetaxel for metastatic hormone-sensitive prostate cancer was allowed. Randomization was stratified by site of metastases and prior docetaxel. All available clinical samples were retrospectively tested for BRCA mutational status with the FoundationOne CDx and FoundationOne Liquid CDx tests (Foundation Medicine, Inc.).

The major efficacy outcome measure was investigator-assessed radiological progression-free survival (rPFS) per RECIST version 1.1 for soft tissue and Prostate Cancer Working Group criteria for bone lesions. Overall survival (OS) was an additional endpoint.

A statistically significant improvement in rPFS for olaparib with abiraterone compared to placebo with abiraterone in the intent-to-treat (ITT) population was observed. An exploratory subgroup analysis in the 85 patients with BRCAm (11% of ITT population) demonstrated a median rPFS that was not reached in the olaparib with abiraterone arm compared to 8 months (95% CI: 6, 15) for those receiving placebo with abiraterone (hazard ratio [HR] 0.24 [95% CI: 0.12, 0.45]). The OS HR in these patients was 0.30 (95% CI: 0.15, 0.59). In the 711 patients (89% of ITT population) without BRCAm, the rPFS HR was 0.77 (95% CI: 0.63, 0.96) and the OS HR was 0.92 (95% CI: 0.74, 1.14), suggesting that the improvement in rPFS observed in the ITT population was primarily attributable to patients with BRCAm.

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%). Seventy-two patients (18%) required at least one blood transfusion and 46 (12%) required multiple transfusions.

The recommended olaparib dose is 300 mg taken orally twice daily with or without food. The recommended abiraterone dose is 1000 mg taken orally once daily. Abiraterone should be administered with prednisone or prednisolone 5 mg orally twice daily. Patients should also receive a GnRH analog concurrently or should have had a prior bilateral orchiectomy.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

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