Immune Checkpoint Inhibitors
Daniel P. Petrylak, MD, explores immune checkpoint inhibitors for the management of bladder cancer, especially metastatic urothelial carcinoma.
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Talks by Daniel P. Petrylak, MD
The Use of Antibody-drug Conjugates in Treating Advanced Urothelial Cancer
Dr. Daniel P. Petrylak discusses using antibody-drug conjugates (ADCs) in the treatment of advanced urothelial cancer.
Read MoreEfficacy of Enzalutamide Plus ADT in Men with De Novo (M1) mHSPC Versus Progression to mHSPC: Post Hoc Analysis of the Phase III ARCHES Trial
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, presents data analysis from the phase III ARCHES trial showing the efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC). He asserts that urologists should be using next generation anti-androgens more often, citing the fact that only about half of patients are being offered such therapies at the time of mHSPC diagnosis. Dr. Petrylak outlines three reasons for this, including lack of access (driven by high cost and staffing availability), lack of understanding of the data, and lack of education. He then summarizes the ARCHES trial specifications, patient characteristics, and the primary endpoint radiographic progression-free survival (rPFS) data, which demonstrate favored outcomes with ENZA combined with ADT, while specifying that mature overall survival (OS) data is not yet available. Dr. Petrylak then discusses secondary endpoint data, which demonstrate that time to prostate-specific antigen (PSA) progression was significantly better in patients who received ENZA and ADT; similarly, ENZA and ADT reduced the risk of starting a new antineoplastic therapy by 72 percent compared with a placebo and ADT. Data also showed patient benefit in terms of time to first symptomatic skeletal event (SSE) as well as time to castration resistance. Dr. Petrylak addresses the question of disease volume in determining which patients ought to receive these next-generation treatments. He examines rPFS across patient subgroups, from patients with just one metastasis all the way up to those with over six metastases, and asserts that all patients across these groups benefited from the ENZA and ADT therapy, dispelling myths that low-volume patients should not be receiving next-generation treatments. Dr. Petrylak concludes that, for patients with castration-sensitive prostate cancer (CSPC), ENZA used with ADT improves rPFS over ADT alone and that the effect is consistent over all volumes of disease, again stipulating that the OS data is maturing, with additional data expected later this year.
Read MoreUpdates on PSMA Imaging and PSMA CAR T Therapy
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.
Read MoreRole of PARP Inhibitors in Prostate 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 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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