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

FDA Approves Olaparib Plus Abiraterone and Prednisone or Prednisolone for BRCA-Variant, Metastatic, Castration-Resistant Prostate Cancer

Efficacy was evaluated in the PROpel trial (NCT03732820) of 796 patients with mCRPC. Patients were randomized 1:1 to receive either olaparib plus abiraterone or placebo plus abiraterone and also prednisone or prednisolone. Patients were required to have had orchiectomy or 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 permitted. Randomization was stratified by metastasis site and prior docetaxel. All clinical samples were retrospectively tested for BRCA variation status with the FoundationOne® CDx and liquid CDx tests.

The major efficacy outcome measure was investigator-assessed radiologic 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.

Researchers observed a statistically significant improvement in rPFS with olaparib plus abiraterone compared to placebo plus abiraterone in the intent-to-treat (ITT) population. An exploratory subgroup analysis in the 85 patients with BRCAm (11% of the ITT population) demonstrated a median rPFS that was not reached in the olaparib plus abiraterone arm compared to eight months (95% CI = 6, 15) for those receiving placebo plus abiraterone (hazard ratio [HR] 0.24 [95% CI = 0.12, 0.45]). The OS HR for patients receiving olaparib plus abiraterone and for those receiving placebo plus abiraterone was 0.30 (95% CI = 0.15, 0.59). In the 711 patients (89% of the 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 reported in at least 10% of patients treated with 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 1,000 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 have had a prior bilateral orchiectomy.

View the full prescribing information for olaparib.

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

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.