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

Innovations in Bladder Cancer: Strategies for Improving Outcomes Across the Disease Continuum

Daniel P. Petrylak, MD, discusses recent advancements in bladder cancer management, highlighting the evolving treatment landscape and the integration of novel therapies. In this 10-minute talk, Petrylak notes a paradigm shift in treating metastatic bladder cancer, moving beyond traditional platinum-based chemotherapies such as gemcitabine and cisplatin, toward immune checkpoint inhibitors.

Petrylak shares trials exploring new therapeutic strategies, such as integrating agents into neoadjuvant and adjuvant settings. For patients ineligible for platinum-based chemotherapy, new protocols involving EV and pembrolizumab provide promising alternatives.

The presentation emphasizes future research’s importance in optimizing treatment sequencing, improving bladder preservation, and minimizing toxicity. With survival rates for metastatic bladder cancer doubling in recent years, ongoing trials are expected to further refine therapeutic strategies and define the next era of bladder cancer care.

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Novel Ways of Targeting the Androgen Receptor

Daniel P. Petrylak, MD, explores novel approaches for targeting the androgen receptor (AR) in prostate cancer, highlighting that around 90% of prostate cancer specimens express the androgen receptor, which persists through castrate resistance.

In this 7-minute talk, Dr. Petrylak focuses on targeting the AR ligand-binding domain with molecules known as proteolysis-targeting chimeras (PROTACs). Laboratory findings reveal that PROTACs can degrade AR variants resistant to traditional therapies like enzalutamide, showing efficacy against androgen gene amplification mutations.

He shares that ARV-110, a PROTAC developed for clinical use, showed promise in phase 1 trials with castration-resistant prostate cancer patients. However, due to significant side effects, the ARV-110 trials were abandoned in favor of a newer compound, ARV-766. While ARV-110 has demonstrated efficacy in castration-resistant prostate cancer, ARV-766 offers a broader range of AR degradation with improved patient tolerance, making it the preferred candidate for continued clinical evaluation.

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PARPi in mCRPC

Daniel P. Petrylak, MD, Yale University Cancer Center, New Haven, Connecticut, summarizes the current and future role of PARP inhibitors in mCRPC, providing valuable insights into their clinical application and potential to improve patient outcomes.

In this 9-minute presentation, Dr. Henderson highlights direct costs such as medications, hospital stays, and physician fees, as well as indirect costs including lost income and travel expenses. He emphasizes that these financial strains can lead to treatment non-adherence, delayed care, and worsened clinical outcomes.

Dr. Henderson discusses various strategies and interventions to address these challenges, underscoring the importance of policy changes at the institutional and governmental levels to improve access to affordable care.

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PET Tumor Board: Case #6

In this discussion, E. David Crawford, MD, Jack A. Vickers Director of Prostate Research and Professor of Urology at the University of California, San Diego, leads a discussion of the case study of a 63 year old patient with a strong family history of prostate cancer. He presents this case study to a panel of experts comprised of:

Wayne G. Brisbane, MD – Assistant Professor of Urology at the University of California, Los Angeles.
Phillip J. Koo, MD – Division Chief of Diagnostic Imaging and Northwest Region Oncology Physician Executive at the Banner MD Anderson Cancer Center.
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.

Dr. Crawford informs the panel that the patient, a physician with a history of low-grade prostate cancer, initially presented with a PSA of 4.9 ng/ml, his germline test was negative, and his MRI revealed a 40g prostate with a PI-RADS 3 lesion at the left base. After a negative SelectMDx scan and low-risk OncotypeDX score, along with a course of finasteride which lowered his PSA to 1.43 ng/ml, Dr. Crawford asks the panel to weigh in on further steps.

Dr. Brisbane suggests exploring reclassifying the patient’s risk score, given his family history, in order to qualify them for a PSMA. Dr. Petrylak supports the suggestion, mentioning that it has been common practice to reimage patients after finasteride use.

Dr. Crawford shows the results from the patient’s POSLUMA scan which showed uptake in multiple foci. Dr. Koo digs into the results, noting that there are alternate explanations for the results showing multiple uptakes. Given the patient’s risk profile, the panel suggests a confirmatory biopsy of the prostate in the highest activity areas.

Dr. Crawford reveals that the patient’s confirmatory biopsies showed the presence of Gleason 6 (3+3) prostate cancer in the uptake areas. Given the discordance between the biopsies and the scans, the panel discusses possible next steps, including sending the biopsy samples for Decipher testing, treating the patient with targeted focal therapy, and options for whole-gland therapy. The panel also discusses the dangers of over-reliance on scan results in treatment selection and cautions against over-treatment.

This is the sixth in a series of discussions on PSMA PET supported by Blue Earth Diagnostics. For the first installment, click here. For the second installment, click here. For the third installment, click here. For the fourth installment, click here. For the fifth installment, click here.

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Clinical Trials in MIBC and NMIBC

Daniel P. Petrylak, MD, discusses advancements in treating urothelial carcinoma, emphasizing innovative therapies for BCG-refractory, recurrent, and metastatic disease.

In this 10-minute talk, Petrylak highlights Dr. Neil Shore’s INSTIL trial, a significant phase 3 study evaluating the adenovirus interferon agent nadofaragene firadenovec. Dr. Petrylak also discusses how immune checkpoint inhibitors, such as pembrolizumab, are moving into early-stage treatment and combined with BCG for non-cystectomy patients.

The discussion transitions to innovative drug delivery systems, such as a “pretzel” device designed for intravesical drug release.
Dr. Petrylak shares new trials in treating metastatic carcinoma that focus on minimizing side effects linked to conventional drugs like enfortumab vedotin by introducing smaller, less immunogenic agents. These trials, including a DEVAL phase 1 dose-escalation study, underscore the importance of these targeted innovations in battling this challenging cancer.

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