Olaparib Approved by FDA for Metastatic HRR-Mutated Castration-Resistant Prostate Cancer
Posted: Friday, May 22, 2020
On May 19, the U.S. Food and Drug Administration (FDA) approved the PARP inhibitor olaparib (Lynparza) for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer. In the United States, two FDA-approved companion diagnostic tests, FoundationOne CDX for HRR-gene alterations and BRACAnalysis CDX for BRCA1 and BRCA2 mutations, will be used to identify treatment eligibility.
The FDA approval was based on results from the prospective, multicenter, open-label phase III PROfound trial. Patients were divided into two cohorts based on their HRR-gene mutation status. Patients with BRCA1, BRCA2, or ATM mutations were randomly assigned to cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned to cohort B (n = 142); and patients with co-mutations were assigned to cohort A.
In cohort A, the median radiologic progression-free survival was 7.4 months with olaparib versus 3.6 months with investigator’s choice of either enzalutamide or abiraterone acetate (hazard ratio [HR] = 0.34; 95% confidence interval [CI] = 0.25–0.47; P < .0001). In addition, the median overall survival was 19.1 months with olaparib versus 14.7 months without (HR = 0.69; 95% CI = 0.50–0.97, P = .0175). In cohorts A and B, the median radiologic progression-free survival with olaparib compared with enzalutamide or abiraterone acetate was 5.8 months versus 3.5 months (HR = 0.49; 95% CI = 0.38–0.63; P = .0001).
The most common adverse reactions in 10% or more of patients receiving olaparib included anemia, nausea, fatigue/asthenia, decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. In addition, venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients in the olaparib arm compared with 3.1% of patients receiving enzalutamide or abiraterone.
The recommended olaparib oral dose is 300 mg twice daily, with or without food. For full prescribing information visit accessdata.fda.gov.