Daniel P. Petrylak, MD, presented “Role of PARP Inhibitors in Prostate Cancer” during the 31st International Prostate Cancer Update in July 2021 in Snowbird, Utah.

How to cite: Petrylak, Daniel P. “Role of PARP Inhibitors in Prostate Cancer.” July 2021. Accessed Jul 2024. https://grandroundsinurology.com/role-of-parp-inhibitors-in-prostate-cancer/

Role of PARP Inhibitors in Prostate Cancer – Summary

Daniel P. Petrylak, MD, Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center in New Haven, Connecticut, discusses PARP inhibitors for castrate-resistant prostate cancer (CRPC). He begins by considering the relevant pathogenic germline mutations, outlining how PARP inhibitors function and presenting studies demonstrating their effectiveness. He notes that the 2015 TOPARP study was the first to suggest that PARP inhibitors could be used to treat metastatic CRPC (mCRPC). Dr. Petrylak then discusses phase III of the PROfound study which found that BRCA 1 and 2 mutations responded best to PARP. In describing the clinical implications, Dr. Petrylak reviews recently FDA-approved PARP inhibitors including olaparib and rucaparib. Olaparib was approved for treatment of homologous recombination repair (HRR) gene-mutated or deleterious germline mCRPC in patients who have progressed following prior treatment with enzalutamide or abiraterone. Rucaparib received accelerated approval for BRCA-mutated mCRPC in patients who have been treated with androgen receptor directed therapy and a taxane-based chemotherapy. Lastly, Dr. Petrylak comments on PARP inhibitor toxicities which include anemia, thrombocytopenia, and neutropenia and may necessitate infusions to help the patient’s blood count. He concludes that PARP inhibition is effective in patients with some DNA repair mutations but may be less effective on ATM mutations.

About The 31st Annual International Prostate Cancer Update:

The International Prostate Cancer Update (IPCU), founded in 1990, is a multi-day CME conference focused on prostate cancer treatment updates with expert, international faculty. It is led by expert physicians and is designed for urologists, medical oncologists, radiation oncologists, and other healthcare professionals involved in the diagnosis and treatment of prostate cancer. Dr. Petrylak delivered this educational activity during the 31st iteration of the meeting in July 2021 in Snowbird, Utah.

ABOUT THE AUTHOR

Daniel P. Petrylak, MD, leads the genitourinary cancers medical oncology team at Smilow Cancer Hospital as director of the genitourinary cancer research group, professor, and co-director of the Cancer Signaling Network program. Dr. Petrylak joined Yale from Herbert Irving Cancer Center at Columbia University Medical Center with New York-Presbyterian Hospital, where he served as Professor of Medicine (Medical Oncology) and Urology and began his appointment in September of 2012. Dr. Petrylak is a member of the American Association for Cancer Research (AACR), American Society for Clinical Oncology (ASCO), American College of Physicians (ACP), American Association for the Advancement of Science (AAAS), American Urological Association (AUA), and the Southwest Oncology Group (SWOG). After serving for more than 20 years as the advanced bladder chair for SWOG, Dr. Petrylak is now the Vice Chair of the Genitourinary Committee. He additionally has led multiple national and international studies in prostate and bladder cancer.

Dr. Petrylak’s research interests span both prostate and bladder cancer. He led an investigator-initiated trial of docetaxel and estramustine in castration resistant prostate cancer. The results of this study supported a phase 3 trial of this combination in SWOG led by Dr. Petrylak, which in turn, supported the FDA approval of docetaxel for castration resistant prostate cancer. This was one of the first two trials to demonstrate a survival benefit in this state of disease. Dr. Petrylak has also been instrumental in the development of immunotherapy and targeted therapies for refractory bladder cancer. His work with Enfortumab Vedotin has supported the accelerated and full FDA approval of this drug.

Dr. Petrylak received his undergraduate degree from Columbia College and his medical degree from Case Western University School of Medicine. He completed his internship and residency at Albert Einstein College of Medicine and his fellowship in medical oncology at Memorial Sloan-Kettering Cancer Center. He has authored more than 200 peer-reviewed articles and book chapters on prostate and bladder cancer research outcomes.