While the development of advanced prostate cancers is largely influenced by androgen receptor (AR) signaling, DNA-damage response (DDR) pathways also contribute to disease progression. AR axis-targeted therapies (ARATs) have been the standard of care for first-line mCRPC. Inhibiting PARP activity is an effective strategy for targeting malignant cells with limited DNA repair capacity due to DDR gene mutations, leading to synthetic lethality. There may be a synergy between ARATs and PARP inhibitors (PARPi), as ARATs can induce HRR deficiencies and PARP inhibitors can increase the activity of ARATs through AR-dependent transcription. Recent clinical trial results have demonstrated that the combination of PARPi with ARATs is safe and effective for the first-line treatment of patients with mCRPC, with 3 combinations now FDA-approved: olaparib + abiraterone, talazoparib + enzalutamide, and niraparib + abiraterone.
This activity will provide expert contextualization of evidence from first-line mCRPC clinical trials exploring these combinations, including insights about the differentiation of both treatment and patient selection, as well as management of treatment-related toxicities. Given the differences in approvals and guidelines between the US and European context, this Ryder Cup themed Expert Panel Discussion will compare and contrast the approach in both regions, giving participants comprehensive education on how best to incorporate these combinations into clinical practice. This activity is designed to bring insights presented at major conferences this year to clinicians treating patients with mCRPC, as well as contrast the different global approaches to the disease so clinicians can keep pace with this fast-moving field.