Daniel P. Petrylak, MD

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

Updates on PSMA Imaging and PSMA CAR T Therapy

Posted by | Oct 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, discusses CAR T therapy for prostate cancer and the ways in which its efficacy is impacted by tumor type and stem memory T cells (TSCM). He begins by reviewing the VISION Trial of LuPSMA which found a 40% reduction in the risk of death and 4-month improvement in median overall survival (OS) versus standard of care (SOC) alone. He also looks at the FDA approval of PYLARIFY in May 2021, the first commercially available PSMA PET imaging agent for prostate cancer. Dr. Petrylak then poses the question of how to combine immunotherapy with PSMA. He suggests that the answer may exist in CAR T therapy despite its historically poor results in solid tumors, and discusses the different types of CAR T cells along a spectrum of less differentiated, self-renewing, and long-lived cells to more differentiated, less stem-like cells. Dr. Petrylak states that TSCM, which exist on the less differentiated side of the spectrum, are key to CAR T therapy’s success in solid tumors based on evidence from a study using a TSCM-based approach that found 100% tumor elimination in animals at standard and low doses after 2 weeks. He reviews early information on a Phase I trial of TSCM based CAR T therapy on mCRPC patients which appears to have positive early results. Dr. Petrylak concludes that PSMA is proving to be an excellent target for imaging and therapy in mCRPC and CAR T therapy may be able to enhance treatment as well.

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Role of PARP Inhibitors in Prostate Cancer

Posted by | Sep 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, 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.

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Future Trials of Lutetium-177

Posted by | 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, 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.

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Radium-223 Trial Updates

Posted by | 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.

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Enfortumab Vedotin for Previously Treated Advanced Urothelial Carcinoma

Enfortumab Vedotin for Previously Treated Advanced Urothelial Carcinoma

Posted by | 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.

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