Daniel P. Petrylak, MD, presented “Future Trials of Lutetium-177” during the 31st International Prostate Cancer Update in July 2021 in Snowbird, Utah.
How to cite: Petrylak, Daniel P. “Future Trials of Lutetium-177.” July 2021. Accessed Jul 2024. https://grandroundsinurology.com/future-trials-of-lutetium-177/
Future Trials of Lutetium-177 – 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 the future of lutetium-based trials. He argues in favor of the use of lutetium-177 (177Lu)–PSMA-617 earlier in the treatment cycle for prostate cancer. Dr. Petrylak examines the disease states for non-castrate and castration-resistant prostate cancer (CRPC) and concludes that there is a better hazard ratio in terms of survival when drugs such as abiraterone acetate, enzalutamide, apalutamide, and docetaxel are used earlier in disease progression. Dr. Petrylak posits that it makes sense, then, to use 177Lu-PSMA-617 in the earlier setting as well. He discusses the scientific rationale for earlier use of 177Lu-PSMA-617, including the fact that fewer genomic alterations exist in earlier disease stages, alterations that may later lead to resistance to radiation therapy (RT) and to other treatments. Dr. Petrylak explains that the expression of prostate-specific membrane antigen (PSMA) increases with androgen deprivation therapy (ADT), potentially leading to better patient outcomes. Additionally, ADT inhibits DNA strand break repair and this can synergize with RT. He then cites a trial being designed to examine the earlier use of 177Lu-PSMA-617 in men with untreated or minimally-treated metastatic hormone-sensitive prostate cancer (mHSPC), who will be randomized on a 1:1 basis and given 177Lu-PSMA-617 for six cycles plus best standard of care or given best standard of care. Dr. Petrylak explains the study design as well as its primary endpoint (the time from randomization to the date of radiographic progression-free survival) and secondary endpoints. He then discusses dose, administration, and standard of care. Dr. Petrylak concludes by asserting that this is an exciting trial and urges his colleagues to participate. Beyond this current trial, Dr. Petrylak theorizes about potential combinations with Lutetium-based compounds, including immunotherapy, citing the abscopal effect; poly adenosine diphosphate-ribose polymerase (PARP) inhibitors, though this may be limited by cytopenias; as well as the implementation of next-generation antiandrogens, which can upregulate PSMA. Dr. Petrylak concludes by calling this data exciting and asserting it will be a basis for future clinical trials.
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.
