Dr. Schweizer on the Role of Olaparib in Non–BRCA-Mutant mCRPC

Michael Schweizer, MD, physician, Seattle Cancer Care Alliance, assistant professor, Division of Medical Oncology, University of Washington School of Medicine, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the role of olaparib (Lynparza) in patients with non–BRCA-mutant metastatic castration-resistant prostate cancer (mCRPC).

The phase 3 PROfound trial demonstrated prolonged progression-free survival (PFS) with the PARP inhibitor olaparib in men with mCRPC who had disease progression on enzalutamide (Xtandi) or abiraterone acetate (Zytiga). Cohort A consisted of patients with at least 1 alteration in BRCA1, BRCA2, or ATM, and cohort B comprised patients with at least one alteration in any of the other 12 prespecified genes. 

Although olaparib demonstrated a significant radiographic PFS benefit in the overall patient population and in cohort A, radiographic PFS findings for cohort B did not show a significant benefit with olaparib vs the control regimen for patients with non–BRCA-mutant disease, says Schweizer.

Although the trial was not powered to analyze differences in radiographic PFS between specific genetic mutations, these data highlight the need for additional research to determine whether olaparib should be considered for patients with mCRPC who lack BRCA1/2 mutations, Schweizer says. As it stands, olaparib can be utilized for these patients; however, more standard options that have demonstrated efficacy across genomic subtypes should be preferred, concludes Schweizer.