Dr. Agarwal on the FDA Approval of Olaparib in HRR-Mutant mCRPC

Neeraj Agarwal, MD, professor of medicine, and director of the Genitourinary Oncology Program, Huntsman Cancer Institute, discusses the FDA approval of olaparib (Lynparza) as a treatment for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga).

The approval is based on findings from the phase 3 PROfound trial, which showed that the PARP inhibitor olaparib induced a 66% reduction in the risk of disease progression or death compared with abiraterone acetate or enzalutamide (HR, 0.34; 95% CI, 0.25-0.47; P <.001) in patients with BRCA1/2- or ATM-mutant mCRPC.

Overall, the trial showed that olaparib demonstrated a 51% reduction in the risk of disease progression or death versus either of the antiandrogen agents (HR, 0.49; 95% CI, 0.38-0.63; P <.001) in the entire population of patients with HRR-mutant mCRPC who had mutations in genes for BRCA1/2, ATM, CDK12, or 11 other HRR-mutated genes. It is difficult to tease out the benefit of the PARP inhibitor in individual subsets, such as those with ATM mutations, says Agarwal. However, the regulatory decision is great news for patients with HRR-mutant mCRPC, concludes Agarwal.