Acting on Actionable Mutations in Metastatic Prostate Cancer

Abstract

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. Approximately a quarter of men with metastatic castration-resistant prostate cancer have genomic alterations within the homologous recombination repair pathway with poly (ADP-ribose) polymerase (PARP) inhibitors as corresponding treatment options. How to incorporate genomic information and associated therapeutic options into treatment decision making and sequencing of therapies in prostate cancer remains challenging. Men with BRCA2 alterations seem to derive the most benefit from PARP inhibitors, and although early treatment in combination with standard therapies has not yet shown an overall survival benefit, there may be other benefits to incorporating PARP inhibitors early for some men.