Olaparib Gains FDA Approval for BRCA+ mCRPC


The FDA has approved olaparib for patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.

Olaparib Gains FDA Approval for BRCA+ mCRPC

Olaparib Gains FDA Approval for BRCA+ mCRPC

The FDA has granted olaparib (Lynparza) in combination with abiraterone (Zytiga) and prednisone (or prednisolone) approval for the treatment of patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.1,2

Findings from the phase 3 PROpel trial (NCT03732820) support the approval. Findings showed that among 796 patients who were randomly assigned to receive either olaparib or placebo with abiraterone in combination with prednisone or prednisolone, those who received the experimental regimen achieved superior radiographic progression-free survival (rPFS) outcomes. Specifically, in an exploratory subgroup analysis of those with BRCA-mutated disease (n = 85; 11%), those who received olaparib (n = 47) achieved a median rPFS that was not reached (NR) at data cutoff compared with 8 months (95% CI, 6-15) in the control arm (n = 37) for an HR of 0.24 (95% CI, 0.12-0.45). Moreover, the HR for overall survival (OS) was 0.30 (95% CI, 0.15-0.59) with the median OS NR in the olaparib arm compared with 23 months (95% CI, 18-34) in the control arm.2

Among the 711 patients without a BRCA-mutation (89%), the HR for rPFS was 0.77 (95% CI, 0.63-0.96) and the HR for OS was 0.92 (95% CI, 0.74-1.14). According to the FDA, these findings suggest that the improvement in rPFS in the intention-to-treat population was primarily driven by patients with BRCA-positive disease.1

The recommended dose of olaparib is 300 mg twice daily. It can be taken with or without food. Patients receiving this medication should have also received a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. For patients who have moderate renal impairment, the recommended dose is 200 mg twice daily.2

Of note, olaparib comes with warnings for myelodysplastic syndrome/acute myeloid leukemia, pneumonitis, venous thromboembolism, and embryo-fetal toxicity.2

The most common adverse events that were reported with the experimental regimen in this trial were anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%). In addition, 72 patients needed to undergo at least 1 blood transfusion (18%) and 46 patients (12%) needed multiple transfusion during their treatment.1

In the event of an adverse event (AE), the first recommended dose reduction is 250 mg twice daily. If another is required, then 200 mg twice daily is advised. It is advised that the concomitant use of a strong or moderate CYP3A inhibitors be avoided with this treatment.2


  1. FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. FDA. News release. May 31, 2023. Accessed May 31, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-abiraterone-and-prednisone-or-prednisolone-brca-mutated-metastatic-castration
  2. Lynparza. Prescribing information. AstraZeneca; 2023. Accessed May 31, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208558s025lbl.pdf
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