Daniel P. Petrylak, MD

Daniel P. Petrylak, MD

Yale University Cancer Center

New Haven, Connecticut

Daniel P. Petrylak, MD, is currently 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. He is a recognized international leader in the urology field. He earned his MD at Case Western Reserve University School of Medicine in Cleveland Ohio. He then went on to complete his Internal Medicine Residency at Albert Einstein College of Medicine/Jacobi Medical Center in the Bronx, and his fellowship at Memorial Sloan Kettering Cancer Center in New York. Dr. Petrylak has served as principal investigator (PI) or co-PI on several SWOG clinical trials for genitourinary cancers. Most notably, he served as the PI for a randomized trial that led to the FDA approval of docetaxel in hormone refractory prostate cancer. He also helped to design and served as PI for the SPARC trial, an international registration trial evaluating satraplatin as a second-line therapy for hormone refractory prostate cancer. Dr. Petrylak served on the program committees for the annual meetings of the American Urological Association from 2003-2011, and for the American Society of Clinical Oncology from 1995-1997 and 2001-2003. He also has served as a committee member for the Devices and Immunologicals section of the FDA. He has published extensively in the New England Journal of Medicine, Journal of Clinical Oncology, Journal of the National Cancer Institute, Cancer Research, and Clinical Cancer Research.

Disclosures:

Articles by Daniel P. Petrylak, MD

Enfortumab Vedotin for Previously Treated Advanced Urothelial Carcinoma

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, summarizes his article on the EV-301 study of enfortumab vedotin and its role in making the drug a standard treatment option for patients with urothelial cancer. In 2012, Dr. Petrylak began working on a phase 1 trial of enfortumab which found that the drug had about a 40% response rate in patients with or without checkpoint surgery. He then worked on the EV-201 phase 2 trial, which found about a 40% response rate in patients previously treated with either a platinum-based chemotherapy or checkpoint inhibitor. Dr. Petrylak also worked on the phase 3 study (EV-301), which randomized patients to receive either enfortumab vedotin or standard chemotherapy and found significant overall survival benefits as well as a response rate of about 40% in the enfortumab arm. By confirming phase 1 and phase 2 data, this study earned enfortumab vedotin accelerated FDA approval. Dr. Petrylak does note that the drug has some side effects, including neuropathy and rashes. The video ends with a question and answer session conducted by E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology. Drs. Petrylak and Crawford discuss plans to use enfortumab vedotin earlier in the treatment process, and Dr. Petrylak observes that many studies are working on exactly that, including one looking at using enfortumab with pembrolizumab as a first-line treatment.

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Sacituzumab Govitecan Given Accelerated FDA Approval for Advanced Urothelial Cancer

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, discusses the FDA’s recent approval of sacituzumab govitecan for metastatic urothelial carcinoma. He notes how previously, treatment options were limited for patients who failed initial chemotherapy. Dr. Petrylak then describes how the new antibody drug conjugate sacituzumab govitecan acts as a “smart bomb” in the way it can recognize cancer markers and deliver chemotherapy directly to affected cells. He then describes the trial that led to the approval of sacituzumab govitecan, including differences between it and enfortumab vedotin, how treatment has been combined with both drugs, and how it is expanding the spectrum of treatments for advanced urothelial carcinoma. Dr. Petrylak also discusses side effects of the drug and potential next steps for its use in treatment.

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Management of BCG-Unresponsive Cystectomy-Ineligible Bladder Cancer Patients: Pembrolizumab

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 alternatives to bacillus Calmette-Guerin (BCG) immunotherapy for non-muscle invasive bladder cancer (NMIBC), focusing on pembrolizumab. Dr. Petrylak gives an overview of NMIBC and of NMIBC management with BCG immunotherapy. He explains that BCG immunotherapy is standard of care for this difficult-to-treat disease state and has proven capable of reducing recurrence, progression, and death rates, but that there is a subset of patients who experience BCG failure. Dr. Petrylak describes the different kinds of BCG failure, including BCG-relapsing, BCG-intolerant, BCG-refractory, and BCG-resistant disease, and then discusses the limited treatments currently available for these patients. He observes that intravesical chemotherapies have not proven highly efficacious for NMIBC, but that immune checkpoint inhibitors like pembrolizumab show significant promise. Dr. Petrylak reviews the KEYNOTE-057 trial, which found that immune checkpoint therapy with pembrolizumab can lead to complete responses in 40% of patients, and the SWOG S1605 trial, which did not reach its endpoint but found a complete response to immune checkpoint therapy with atezolizumab at 6 months in 27% of patients. He concludes by discussing other ongoing and future trials to further evaluate checkpoint inhibitors for NMIBC.

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Immunotherapy Trials

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, discusses the various trials currently evaluating immunotherapies for castration-resistant prostate cancer (CRPC) and metastatic castration-resistant prostate cancer (mCRPC). To this point, Dr. Petrylak explains, there have not been many obvious survival benefits from immunotherapy in prostate cancer, except in patients with specific tumor mutations; therefore, sipuleucel-T and pembrolizumab are currently the only FDA-approved immunotherapeutic agents for CRPC. Fortunately, numerous trials are underway that study more effective ways to use immunotherapies for prostate cancer, including trials to improve sipuleucel-T, trials researching vaccine-based immunotherapy regimens, and numerous combination therapy trials. Dr. Petrylak also discusses alternative approaches to immune treatment, including CAR-T cell and BiTE studies in CRPC.

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Theranostics & Radiopharmaceutical Trials

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, reviews several studies in which radium-223 is used both alone and in combination with other treatments for prostate cancer. Since radium-223 is an alpha particle, it requires fewer hits to damage DNA, offering an advantage over beta particles. Dr. Petrylak further explains the benefits of theranostics which deliver isotopes directly to the tumor site. He concludes that radium-223 is effective in treating metastatic castration-resistant prostate cancer (mCRPC), but cautions that until potential toxicity levels are better understood, combining radium-223 with either abiraterone or prednisone is not advised.

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