Dr. Petrylak on Pivotal PARP Inhibitor Trials in mCRPC With DNA Repair Mutations

September 28, 2020

Daniel P. Petrylak, MD, discusses the pivotal trials that have led to the regulatory approvals of the PARP inhibitors olaparib and rucaparib in patients with metastatic castration-resistant prostate cancer and DNA repair mutations.

Daniel P. Petrylak, MD, professor of medicine and urology and co-leader of Cancer Signaling Networks with Yale Cancer Center, as well as a 2017 Giant of Cancer Care® in Genitourinary Cancers, discusses the pivotal trials that have led to the regulatory approvals of the PARP inhibitors olaparib (Lynparza) and rucaparib (Rubraca) in patients with metastatic castration-resistant prostate cancer (mCRPC) and DNA repair mutations.

Several key trials have examined PARP inhibitors in patients with CRPC, says Petrylak. The phase 3 PROfound trial examined olaparib in patients with either a BRCA1/2 or ATM mutations or those with 12 other homologous recombination repair gene mutations. In the first group, a significant difference in radiographic progression-free survival was observed in favor of olaparib compared with physician’s choice of enzalutamide (Xtandi) or abiraterone acetate (Zytiga).

Similarly, in the phase 2 TRITON2 trial, patients with metastatic CRPC were treated with the PARP inhibitor rucaparib. Results showed a 50.2% response rate across all patients with DNA repair mutations, such as BRCA1/2 or ATM.

Both of these studies led to the approval of olaparib and rucaparib, respectively, in patients with mCRPC and DNA repair mutations, concludes Petrylak.


x