Dr Yu on Factors for PARP Inhibitor Decision-Making in Metastatic Prostate Cancer

"[Selecting a PARP inhibitor] is not just all about efficacy, and it's still not clear that efficacy is definitively better between any PARP inhibitor [vs] another."

Evan Ya-Wen Yu, MD, a medical oncologist and professor in the Division of Oncology at the University of Washington and Fred Hutchinson Cancer Center, discussed key considerations surrounding the tolerability of PARP inhibitors and how their adverse effect (AE) profiles influence treatment decision-making in metastatic prostate cancer.

Yu explained that although efficacy data support the use of PARP inhibitors in select patients with prostate cancer—particularly in those with homologous recombination repair (HRR) gene alterations—these agents are associated with a range of gastrointestinal (GI) and hematologic AEs that should be factored into clinical decision-making. The most frequently reported AEs include low-grade nausea, anorexia, and other mild GI disturbances. Myelosuppression, including anemia and neutropenia, is also common, with talazoparib (Talzenna) in particular demonstrating a more pronounced suppressive effects on bone marrow.

Yu noted that the toxicity profile of each agent should be weighed alongside patient-specific clinical characteristics, such as comorbidities, performance status, and concurrent therapies. For example, patients with preexisting cytopenias or those on other myelosuppressive treatments may be at increased risk for hematologic toxicities and may require close monitoring, dose adjustments, or the selection of an alternative agent.

These considerations support a personalized approach to selecting PARP inhibitors for eligible patients with metastatic prostate cancer, Yu continued. Toxicity profiles play a central role in guiding treatment, as differences in safety and tolerability can significantly impact treatment adherence and long-term outcomes.

Yu emphasized that future comparative studies will be critical to better delineate differences in efficacy and safety across the class, and to further inform individualized treatment decisions for patients with metastatic prostate cancer receiving PARP inhibitors.