Emmanuel S. Antonarakis, MD

EMMANUEL S. ANTONARAKIS, MD, Associate Professor of Oncology, Johns Hopkins University, Baltimore, commented on the state of current knowledge about poly (ADP-ribose) polymerase (PARP) inhibitors in prostate cancer.

“PARP inhibitors are definitely making inroads in the management of patients with advanced prostate cancer with germline or somatic homologous recombination–deficiency mutations. However, it is becoming clear that not all of these mutations will demonstrate equal sensitivity to PARP inhibitors. For example, accumulating data suggest that most men with BRCA1/2 mutations respond quite favorably to these agents, whereas patients with ATM or CDK12 mutations generally do not benefit,” Dr. Antonarakis said.

Unanswered Questions

ACCORDING TO Dr. Antonarakis, additional unanswered questions remain. For instance:“Is biallelic genetic inactivation of homologous recombination required for optimal response to PARP inhibition? Do germline and somatic homologous repair–deficiency mutations in the same gene respond equally?”

Dr. Antonarakis continued: “In addition, most PARP inhibitor trials in prostate cancer have focused on patients with advanced castration-resistant disease. What the field is lacking is studies using PARP inhibitors in metastatic hormone-sensitive disease or in even earlier prostate cancer disease states. The ultimate question is whether PARP inhibitors can be used as initial noncastrating therapy in appropriately selected, genomically defined patients. I would like to see more studies like that in the future.” ■

DISCLOSURE: Dr. Antonarakis is a consultant/advisor to and has received institutional research funding from AstraZeneca, Merck, Clovis, and Janssen.