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This Oncology PER®Spectives™ podcast explores the role of EZH2 in metastatic castration-resistant prostate cancer (mCRPC) progression and its synergy with androgen receptor inhibitors. In this podcast, experts Neeraj Agarwal, MD, FASCO; Himisha Beltran, MD; and Maha Hussain, MD, FACP, FASCO, discuss the management of mCRPC. Acknowledgment of Educational Grant Support This activity is supported by an educational grant from Pfizer Inc. Accreditation/Credit Designation Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians’ Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669, for 1.5 Contact Hours. Instructions on How to Receive Credit Listen to this podcast in its entirety. Go to gotoper.com/credit and enter code: 6947 Answer the evaluation questions. Request credit using the drop-down menu. You may immediately download your certificate. Today’s faculty are: Neeraj Agarwal, MD, FASCO Professor of Medicine Senior Director for Clinical Research HCI Presidential Endowed Chair of Cancer Research Director, Center of Investigational Therapeutics Director, Genitourinary Oncology Program Huntsman Cancer Institute, University of Utah (NCI-CCC) Salt Lake City, UT Disclosures: Grant/Research Support (paid to institution): Arvinas, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GlaxoSmithKline, Immunomedics, Janssen, Lava, Merck, Nektar, Neoleukin, Novartis, Oric, Pfizer, Roche, Sanofi, Seagen, Takeda, Tra-con Himisha Beltran, MD Associate Professor of Medicine Director of Translational Research Within Medical Oncology Harvard Medical School Lank Center for Genitourinary Oncology and the Division of Molecular and Cellular Oncology Dana Farber Cancer Institute Boston, MA Disclosures: Grant/Research Support: Circle Pharma, Daiichi Sankyo, Novartis; Adviser: Amgen, AstraZeneca, Daiichi Sankyo, Novartis Maha Hussain, MD, FACP, FASCO Genevieve E. Teuton Professor of Medicine Professor, Medicine (Hematology/Oncology) Deputy Director Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago, IL Disclosures: Advisory Board: AstraZeneca, Bayer, Convergent Therapeutics, Honoraria: AstraZeneca, Bayer The staff of Physicians’ Education Resource®, LLC, have no relevant financial relationships with ineligible companies. PER® mitigated all COI for faculty, staff, and planners prior to the start of this activity by using a multistep process. Off-Label Disclosure and Disclaimer This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this accredited activity is for continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity. Release Date May 14, 2025 Expiration Date May 14, 2026

In today’s episode, supported by SpringWorks Therapeutics, we spoke with Christopher L. Moertel, MD, about the evolution of treatments for neurofibromatosis type 1 (NF1)–associated plexiform neurofibromas (PN). Dr Moertel is a professor and the Pediatric Neuro-Oncology Fellowship Program director in the Division of Pediatric Hematology/Oncology, a faculty member in the Department of Pediatrics, medical director of the Pediatric Neuro-Oncology and Neurofibromatosis Programs, co-medical director of the Katie Hageboeck Children’s Cancer Research Fund Clinic, clinical neuro-oncology leader of the Brain Tumor Program, and the Kenneth and Betty Jayne Dahlberg Professor at the University of Minnesota School of Medicine in Minneapolis. In our exclusive interview, Dr Moertel discussed the expansion of the NF1-associated PN treatment paradigm to include the MEK inhibitors mirdametinib (Gomekli) and selumetinib (Koselugo); the benefits of offering treatment options in oral formulations; the toxicities associated with MEK inhibitors; the importance of managing these adverse effects to ensure long-term treatment adherence; and the need for continued oncology education to optimize treatment outcomes for this population.

This featured podcast includes a data review and candid conversation with 4 experts on challenges in the current treatment paradigm for hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC) due to endocrine resistance. This session occurred during a satellite symposium held in conjunction with the 42nd Annual Miami Breast Cancer Conference® in March 2025.  ESR1 mutations are a critical mechanism of resistance, spurring the development of next-generation endocrine agents targeting these mutations. These agents including oral selective estrogen receptor degraders (SERDs) and agents with novel mechanisms, including proteolysis-targeting chimeras (PROTACs), which may offer potential improvements over current treatments. This program will review mechanisms of resistance to current endocrine regimens, strategies to overcome this resistance including comparative mechanisms of novel endocrine agents, emerging data from ongoing clinical trials, and expert perspectives on where these new agents may fit into current algorithms.

In today’s episode, supported by Revolution Medicines, we spoke with Kathryn C. Arbour, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, about 2 important abstracts presented at the 2024 AACR Annual Meeting that explore novel RAS-targeted approaches in non–small cell lung cancer (NSCLC). Our discussion focused on early clinical findings with zoldonrasib (RMC-9805) and daraxonrasib (RMC-6236), both of which are RAS(ON) inhibitors under investigation for the treatment of patients with RAS-mutant NSCLC. Zoldonrasib, a KRAS G12D-selective tri-complex inhibitor, was evaluated in a phase 1 trial (NCT06040541) in patients with previously treated, advanced KRAS G12D–mutated solid tumors, including NSCLC. Daraxonrasib, a multi-selective RAS(ON) inhibitor, was highlighted in another phase 1 trial (NCT05379985) in patients with advanced RAS-mutant tumors, including previously treated NSCLC; notably, this AACR presentation focused on the association between early on-treatment circulating tumor DNA level reduction and clinical response with the agent. In this episode, Dr Arbour shared insights into the mechanisms of action behind these therapies, their respective clinical trial designs, and the potential implications that early data with the agents may have for the evolving RAS-mutant NSCLC treatment paradigm.

This expert podcast includes an engaging discussion among 3 experts on fertility care of patients with breast cancer. This program is designed to help clinicians better recognize and take steps to discuss fertility options in premenopausal patients with hormone receptor-positive (HR+) breast cancer to facilitate care for those women who wish to preserve their reproductive potential without impacting outcomes.

In this engaging discussion, Dr. Anna C. Pavlick, a professor at Weill Cornell Medicine and a pioneer in cutaneous oncology, dives into the promising RP1 plus nivolumab combo for advanced melanoma. She highlights key findings from the IGNITE trial, showcasing its potential for patients who haven't responded to previous treatments. Dr. Pavlick emphasizes the combination's strong efficacy and low toxicity, while also touching on the exciting future of oncolytic viruses in melanoma therapy. A must-listen for anyone interested in cutting-edge cancer treatments!

In today’s episode, we had the pleasure of speaking with Jacob Moyer, BS, and Mark Tyson II, MD, MPH, about a real-world study investigating nadofaragene firadenovec in patients with BCG-unresponsive NMIBC. Moyer is a graduate researcher at Mayo Clinic in Scottsdale, Arizona. Tyson is a urologic oncologist and an associate professor of urology at the Mayo Clinic Alix School of Medicine in Arizona. In our exclusive interview, Moyer and Tyson discussed the durable responses achieved with nadofaragene firadenovec in this patient population, the safety profile of this agent, the importance of pretreatment with antispasmodic medication, and the optimal patient population to receive nadofaragene firadenovec.

In today’s episode, we had the pleasure of speaking with Nicole Lamanna, MD, about patient selection considerations for the use of pirtobrutinib (Jaypirca) in the management of chronic lymphocytic leukemia (CLL). Dr Lamanna is a hematologic oncologist at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Irving Medical Center in New York, New York. In our exclusive interview, Dr Lamanna discussed how disease progression, treatment intolerance, and prior therapy exposure inform the decision to initiate pirtobrutinib in patients with CLL. She also highlighted important clinical features that guide the use of noncovalent BTK inhibitors—including sequencing strategies following covalent BTK and BCL-2 inhibitors, and emphasized the importance of balancing treatment efficacy with tolerability to optimize long-term disease management in CLL.

In today’s episode, we had the pleasure of speaking with Daniel P. Petrylak, MD, about Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in metastatic castration-resistant prostate cancer (mCRPC). Dr Petrylak is a professor of medicine (medical oncology) and urology, as well as the chief of Genitourinary Oncology, at Yale School of Medicine and Smilow Cancer Hospital in New Haven, Connecticut. In our exclusive interview, Dr Petrylak discussed the current role for Pluvicto in patients with mCRPC, the safety profile of this radiotherapeutic, the importance of multidisciplinary collaboration when delivering this therapy, and future directions for investigating radioligand therapies in combination with other classes of agents.

In today’s episode, supported by Exact Sciences, we had the pleasure of speaking with Eric Christenson, MD, about the Oncodetect test, which is available for use in molecular residual disease detection in patients with solid tumors. Dr Christenson is an assistant professor of oncology at the Johns Hopkins School of Medicine in Baltimore, Maryland. In our exclusive interview, Dr Christenson discussed the capabilities of Oncodetect, its clinical applications, key findings from the Alpha-CORRECT study, and the prognostic value of this test.