Dr. Grivas on PARP inhibition in Germline and DNA Damage Repair-Mutated mCRPC

Petros Grivas, MD, PhD, physician, Seattle Cancer Care Alliance; associate professor, Department of Medicine, Division of Oncology and clinical director of the Genitourinary Cancers Program, University of Washington School of Medicine; and associate member, Clinical Research Division, Fred Hutchinson Cancer Center, discusses PARP inhibition in patients with germline and somatic DNA damage repair-mutated metastatic castration-resistant prostate cancer.

Lower response rates have been observed with PARP inhibition in patients with germline ATM mutations, but higher response rates have been noted in those with BRCA2 mutations, explains Grivas. Many unanswered questions exist regarding germline versus somatic mutations, monoallelic versus biallelic, loss of heterozygosity or no loss, including whether these parameters could impact response to PARP inhibitors—especially in DNA repair gene mutations, says Grivas.

The PROfound trial, which showed significant activity with olaparib in selected patients with BRCA1/2 and ATM mutations, is not conclusive, but it raises the level of enthusiasm for identifying which patients with germline and somatic DNA damage repair mutations will likely benefit from platinum-based chemotherapy and PARP inhibitors, concludes Grivas.