FDA Approval Insights: Olaparib in HRR-Mutant mCRPC


In our exclusive interview, Neeraj Agarwal, MD, discusses the recent FDA approval of olaparib in homologous recombination repair–mutant metastatic castration-resistant prostate cancer.

Welcome to a very special edition of OncLive® On Air! I’m your host today, Caroline Seymour.

OncLive® On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive® covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Neeraj Agarwal, MD, a professor of medicine, and the director of the Genitourinary Oncology Program at Huntsman Cancer Institute at the University of Utah, to discuss the recent FDA approval of olaparib (Lynparza) in metastatic castration-resistant prostate cancer (mCRPC).

On May 19, 2020, the FDA approved olaparib as a treatment for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene–mutated mCRPC who have progressed following treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga).

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

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, olaparib led to 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).

It is difficult to tease out the benefit of the PARP inhibitor in individual subsets, such as those with ATM mutations, explained Agarwal. However, the regulatory decision is great news for patients with HRR-mutant mCRPC.

On May 28, 2020, the results from the trial were published in the New England Journal of Medicine.

In our exclusive interview, Agarwal, who was also a member of the PROfound trial Global Steering Committee, discussed key efficacy and safety data from the PROfound trial, the importance of genomic sequencing in the metastatic setting, and ongoing research with PARP inhibitors in earlier lines of therapy.

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