Exploiting defects in homologous recombination repair for metastatic, castration-resistant prostate cancer.

The PROfound trial highlights that there is a benefit in testing genes involved in homologous recombination (HR) and forms the rationale for testing in all patients with metastatic, castration-resistant prostate cancer (mCRPC). This trial also demostrates that olaparib improves progression free survival (PFS), objective response rate (ORR), and time to pain progression in patients who harbor alterations in BRCA1, BRCA2, and ATM. These are groundbreaking findings - this is the first trial that demonstrates the efficacy of olaparib versus standard therapy in a genomically-selected patient population with metastatic prostate cancer. Although this trial does not demonstrate improvements in overall survival (OS), we believe that this may be an underestimation based on trial-design. Future studies of olaparib are likely to yield further promising results.