Dr. George on Promise of PARP Inhibitors in Prostate Cancer

Daniel J. George, MD, professor of Medicine and Surgery, member, Duke Cancer Institute, discusses the promise of PARP inhibitors in prostate cancer.

PARP inhibitors hold a lot of promise in patients with homologous recombination deficiency (HRD), particularly those who harbor alterations in BRCA1/2 and PALB2. Other HRD alterations that may be important include CHEK2 and ATM, although the data in this space are less clear, says George.

Some of these mutations are seen at the germline level; therefore, screening patients with metastatic disease for these alterations is recommended. More importantly are tests that can detect somatic alterations, adds George. Although these tests are encouraged, they are not always feasible. In addition to tumor biopsies, cell-free DNA may be another way to assess the biology of a patient’s tumor.

PARP inhibitors are likely to have a role in the treatment of patients with HRD, whether as single agents or in combination, says George. The question is whether they will play a role in patients without HRD. Synthetic lethality may be a way of enabling this, either with radiation or immunotherapy. Trials are ongoing and, if positive, may broaden the accessibility of these agents.