Dr. Petrylak on Pivotal PARP Inhibitor Trials in mCRPC With 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.