Priority Review Granted by FDA to Olaparib in Castration-Resistant Prostate Cancer
Posted: Wednesday, January 22, 2020
On January 20, AstraZeneca and MSD Inc. announced that a supplemental new drug application for olaparib (Lynparza) has been accepted and granted Priority Review in the United States by the U.S. Food and Drug Administration (FDA) for patients with metastatic castration-resistant prostate cancer and deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene mutations who have experienced disease progression after prior treatment with a new hormonal agent.
The submission is based on results from the phase III randomized, open-label PROfound trial, which tested this targeted therapy versus abiraterone or enzalutamide in biomarker-selected patients with metastatic castration-resistant prostate cancer. These patients had a qualifying tumor mutation in 1 of 15 genes involved in the HRR pathway, including among them BRCA1/2, ATM, and CDK12.
The study findings showed a statistically significant and clinically meaningful improvement with olaparib for the primary endpoint of radiographic progression–free survival, improving the time patients with BRCA1/2- or ATM-mutated disease lived without disease progression to a median of 7.4 months vs. 3.6 months for those treated with abiraterone or enzalutamide, and reduced the risk of disease progression or death by 66%. The trial also met the key secondary endpoint of radiographic progression–free survival in the overall HRR-mutant population, where olaparib reduced the risk of disease progression or death by 51% and improved radiographic progression–free survival to a median of 5.8 months vs. 3.5 months for those receiving abiraterone or enzalutamide.
The safety profile of olaparib in the PROfound trial was in line with that observed in prior clinical trials. The most common adverse events occurring in ≥ 20% of patients were anemia, nausea, fatigue/asthenia, decreased appetite, and diarrhea. The most common grade 3 or higher adverse events occurring in ≥ 1% of patients were anemia, fatigue/asthenia, vomiting, dyspnea, urinary tract infection, pulmonary embolism, decreased appetite, diarrhea, back pain, and nausea. A total of 16% of patients who received olaparib discontinued treatment due to adverse events.