On May 31, 2023, the PARP inhibitor olaparib was approved by the U.S. Food and Drug Administration (FDA) with abiraterone and prednisone or prednisolone for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer, as determined by an FDA-approved companion diagnostic test.1
Approval was based on findings from the PROpel trial (ClinicalTrials.gov identifier NCT03732820). In this study, 796 patients with metastatic castration-resistant prostate cancer (intention-to-treat population) were randomly assigned to receive olaparib at 300 mg twice daily (n = 398) or placebo (n = 396) plus abiraterone at 1,000 mg once daily and prednisone or prednisolone at 5 mg twice daily.
Investigator-assessed progression-free survival was significantly improved in the olaparib vs control group in the intention-to-treat population. In an exploratory analysis of the 85 patients with BRCA-mutant disease (11% of the population), median radiographic progression–free survival was not reached in 47 patients in the olaparib group vs 8 months (95% confidence interval [CI] = 6–15 months) in 38 patients in the control group (hazard ratio [HR] = 0.24, 95% CI = 0.12–0.45); median overall survival was not reached vs 23 months (95% CI = 18–34 months; HR = 0.30, 95% CI = 0.15–0.59). Among the 711 patients without BRCA mutation (89% of the population), the hazard ratios were 0.77 (95% CI = 0.63–0.96) for progression-free survival and 0.92 (95% CI = 0.74–1.14) for overall survival.
OF NOTE
Olaparib has warnings/precautions for myelodysplastic syndrome/acute myeloid leukemia; pneumonitis; venous thromboembolism; and embryofetal toxicity.How It Is Used
The recommended regimen is olaparib at 300 mg twice daily, abiraterone at 1,000 mg once daily, and prednisone or prednisolone at 5 mg twice daily; treatment should continue until disease progression or unacceptable toxicity. Patients should have had prior bilateral orchiectomy or concurrently receive a gonadotropin-releasing hormone analog.
Safety Profile
In the PROpel trial, the most common adverse events of any grade in the olaparib group occurring at an incidence of at least 5% higher vs the control group were anemia (48% vs 18%), fatigue (38% vs 30%), nausea (30% vs 14%), diarrhea (19% vs 10%), decreased appetite (16% vs 7%), lymphopenia (14% vs 6%), dizziness (14% vs 7%), and abdominal pain (13% vs 7%). Olaparib was discontinued because of adverse events in 16%, and fatal adverse events were reported in 6% of patients.
Olaparib has warnings/precautions for myelodysplastic syndrome/acute myeloid leukemia; pneumonitis; venous thromboembolism; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving olaparib.
REFERENCE
1. Lynparza (olaparib) tablets prescribing information, AstraZeneca, May 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208558s025lbl.pdf. Accessed June 15, 2023.
