Daniel P. Petrylak, MD

Yale University Cancer Center

New Haven, Connecticut

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.

Disclosures:

Dr. Petrylak has the following disclosures:

Consultant fees: *Ada Cap (Advanced Accelerator Applications), *Amgen, Astellas, AstraZeneca,
Bayer, *Bicycle Therapeutics, *Boehringer Ingelheim, Bristol Myers Squibb, *Clovis
Oncology, *Eli Lilly, Exelixis, Gilead Sciences, *Incyte, Infinity Pharmaceuticals,
Ipsen, *Janssen, Merck & Company Inc, *Mirati, Monopteros, Pfizer,
*Pharmacyclics, Regeneron, *Roche, Sanofi Aventis Pharmaceuticals, Seattle
Genetics, *Urogen

Grant Support: Ada Cap (Advanced Accelerator Applications), *Agensys Inc, Arvinas, Astellas,
AstraZeneca, *Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology,
Daiichi Sankyo Company Limited, *Eisai, *Eli Lilly, Endocyte, Ferring, Genentech,
Gilead Sciences, *Innocrin, *MedImmune, *Medivation, Merck, *Mirati, *Novartis,
Pfizer, *Progenics, *Replimune, *Roche, *Sanofi Aventis, Seattle Genetics

Ownership interest/investment: *Bellicum (Sold 7/2020), *Tyme (sold 10/2019)

*denotes relationships recently terminated

Talks by Daniel P. Petrylak, MD

Radium-223 Trial Updates

Posted by Daniel P. Petrylak, MD | Jul 2021

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, launches his talk with some background on radium-223 before reviewing the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial, including study design, patient demographics, and baseline characteristics. He presents an updated analysis of overall survival (OS) which showed a benefit of 3.6 months compared with a placebo. Dr. Petrylak posits that it makes sense to combine radiation and immunotherapy because of potential synergism, citing the abscopal effect. He then refers to a trial, A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer, addressing the three arms of the trial and presenting survival data, including a waterfall plot demonstrating prostate-specific antigen (PSA) and a very modest objective response rate. Dr. Petrylak discusses the evaluation of the abscopal effect, with trial data not showing PDL1 expression increasing after radium-223; in terms of the abscopal effect, Dr. Petrylak concludes, “it’s just not there.” He further concludes that the trial findings were disappointing. Dr. Petrylak then turns his focus to research on radium-223 with abiraterone/prednisone that found increased patient bone fractures. This finding led to an urgent safety letter being issued, mandating the use of bone-protective agent (BPAs) for at least six weeks before the first injection of radium-223 to reduce fractures. Dr. Petrylak cites data from the EORTC 1333/PEACE III trial which confirms that risk of fractures was well controlled when patients with metastatic castration-resistant prostate cancer (mCRPC) received BPAs, emphasizing the importance of compliance with the BSA recommendations. Dr. Petrylak moves on to cite a study examining radium-223 with chemotherapy (docetaxel) showing significant PSA declines. This research is now part of the DORA trial, which is still recruiting patients nationally. Dr. Petrylak addresses radium-223 dosing, citing investigational trials involving higher doses of radium-223 and extended dosing cycles. He concludes that data support the current regimen of six cycles of radium-223 at the standard dose as the optimal regimen in mCRPC. Dr. Petrylak concludes his discussion by emphasizing that combination trials with docetaxel are ongoing.

Enfortumab Vedotin for Previously Treated Advanced Urothelial Carcinoma

Posted by Daniel P. Petrylak, MD | Apr 2021

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.

Sacituzumab Govitecan Given Accelerated FDA Approval for Advanced Urothelial Cancer

Posted by Daniel P. Petrylak, MD | Apr 2021

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.

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

Posted by Daniel P. Petrylak, MD | Feb 2021

Immunotherapy Trials

Posted by Daniel P. Petrylak, MD | Jul 2020

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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