Home
This site is intended for healthcare professionals
Sign upLog in

mCRPC Synergy Series: Overcoming Resistance and Optimizing Pathways | Part 4: Emerging Non-Chemo Options

Clinical oncology
Medical oncology
Claim CME credit
Share

Description

This program is supported by an independent educational grant from Pfizer. This education program is available to healthcare professionals globally.

This is Part 4 of a four-part on-demand series.

Join prostate cancer experts Dr. Michael Schweizer and Dr. Emmanuel Antonarakis for this accredited, interactive teaching session focused on the latest updates for 2026 in overcoming treatment resistance and optimizing therapeutic pathways in metastatic castration-resistant prostate cancer (mCRPC). Through real-world cases and expert-led discussion, faculty will translate emerging evidence into practical strategies to support sequencing decisions after AR pathway inhibitor (ARPI) progression. This program also includes an interview with a patient advocate from Zero Prostate Cancer, Darrell Wilson.

Credits: AMA PRA Category 1 Credits™ (0.25.00 hours)

Session Overview

Overcoming Resistance and Optimizing Pathways

This case-based session explores how evolving insights into resistance biology can inform more precise, personalized treatment decisions in mCRPC. Faculty will guide learners through common clinical scenarios encountered after ARPI progression, highlighting how biomarkers, emerging mechanisms, and novel non-chemotherapy approaches may shape next steps in care.

  • Review emerging insights into resistance biology beyond DNA repair, including lineage plasticity, AR co-activation, and epigenetic dysregulation, and how these concepts are influencing contemporary mCRPC thinking
  • Discuss the growing translational rationale for targeting epigenetic pathways such as EZH2, including current evidence gaps and implications for future practice
  • Compare novel non-chemotherapy approaches—including radioligand therapies, antibody–drug conjugates, and immunotherapies—and where these modalities may fit within emerging treatment paradigms

Who Should Attend?

This program is designed for healthcare professionals globally involved in the diagnosis, treatment selection, and ongoing management of patients with mCRPC, including:

  • Medical and radiation oncologists
  • Urologists
  • Oncology nurses and nurse practitioners
  • Physician assistants
  • Pharmacists
  • Others involved in prostate cancer care

Faculty

Emmanuel Antonarakis, M.D. is an internationally recognized prostate cancer expert and clinician-scientist with extensive experience in resistance biology, biomarker-driven treatment selection, and translational research guiding precision approaches in mCRPC.

Michael Schweizer, M.D. is a medical oncologist specializing in genitourinary cancers with expertise in advanced prostate cancer, resistance mechanisms, and clinical trials evaluating novel therapeutic strategies in mCRPC.

Darrell Wilson is a patient advocate representing Zero Prostate Cancer.

Program Schedule

Part 1: Decoding Resistance Biology

Apply knowledge of ARPI resistance mechanisms, including epigenetic dysregulation and lineage plasticity, to inform clinical decision-making in mCRPC.

Please click here to access Part 1.

Part 2: Sequencing After ARPI

Formulate and implement evidence-based sequencing strategies for patients progressing on a first-line ARPI, incorporating genomic biomarkers and advanced imaging into individualized treatment plans.

Please click here to access Part 2.

Part 3: Epigenetic Rationale

Incorporate the rationale for targeting epigenetic pathways into treatment planning to extend the clinical benefit of AR-directed therapy in mCRPC.

Please click here to access Part 3.

Part 4: Emerging Non-Chemo Options (Current Module)

Differentiate and apply understanding of mechanisms of action of emerging non-chemotherapy agents, including radioligands, antibody-drug conjugates, and immunotherapies, to guide therapy selection.

Interview with Patient Advocate

Please click here to access the Patient Advocate interview.

Continuing Education Information

Commercial support: This activity received monetary support through an independent education grant from Pfizer.

This continuing education activity will be provided by AffinityCE and MedAll. This activity will provide continuing education credit for physicians. A statement of participation is available to other attendees.

Faculty Disclosure Statement / Conflict of Interest

Emmanuel Antonarakis, MD, has disclosed financial interests or relationships within the past 24 months with the following ineligible companies: Advisory Board/Consultant for Abeona Therapeutics, AstraZeneca, Bayer, DAVA Oncology, EcoR1, Janssen, Johnson & Johnson, Lilly, Merck, MJH Life Sciences, Pfizer, Tango Therapeutics, Tempus, The Medical Educator Consortium, z-Alpha. Grant/Research Support from Bayer, Bristol-Myers Squibb, Clovis, MacroGenics, Merck, Novartis, Orion, Seagen. Honoraria for Binaytara, ClearView, Curium, Fred Hutch Cancer Center, Healthcare Partners, Lilly, Merck. These disclosures are provided in accordance with ACCME standards to ensure transparency and uphold the integrity of continuing education. Dr. Antonarakis does not intend to reference any unlabeled or unapproved uses of products during the presentation.

Michael Schweizer, MD, has disclosed financial interests or relationships within the past 24 months with the following ineligible companies: Advisory Board for Daiichi Sankyo, Fibrogen, J&J, Pfizer, Consultant for Bayer, K36 Therapeutics, Grant/Research Support from Ambrx, AstraZeneca, BMS, Epigenetix, J&J, Lightspeed, Merck, Novartis, Oric Pharmaceuticals, Pfizer, Xencor, Zenith Epigenetics.These disclosures are provided in accordance with ACCME standards to ensure transparency and uphold the integrity of continuing education. Dr. Schweizer does intend to reference unlabeled or unapproved uses of products during the presentation.

Darrell Wilson has disclosed financial interests or relationships within the past 24 months with the following ineligible companies: Patient perspective involvement for Sandoz, Novartis, Pfizer.

AffinityCE staff, MedAll staff, as well as planners and reviewers, have no relevant financial relationships with ineligible companies to disclose.

In compliance with EBAC guidelines, all speakers/ chairpersons participating in this programme have disclosed or indicated potential conflicts of interest which might cause a bias in the presentations. The Organizing Committee/Course Director is responsible for ensuring that all potential conflicts of interest relevant to the event are declared to the audience prior to the CE activities.

Mitigation of Relevant Financial Relationships

AffinityCE adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible companies. Relevant financial relationships were mitigated by the peer review of content by non-conflicted reviewers prior to the commencement of the program.

Activity Accreditation for Health Professions

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physician Assistants

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physician assistants should claim only the credit commensurate with the extent of their participation in the activity.

Nurse Practitioners

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Nurse practitioners should claim only the credit commensurate with the extent of their participation in the activity.

Nurses & Other Professionals

All other health care professionals completing this continuing education activity will be issued a statement of participation indicating the number of hours of continuing education credit. This may be used for professional education CE credit. Please consult your accrediting organization or licensing board for their acceptance of this CE activity.

EBAC® CME Information

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the European Board for Accreditation of Continuing Education for Health Professionals (EBAC)

MedAll is an EBAC accredited provider since 2025. The European Board for Accreditation of Continuing Education for Health Professionals (EBAC) accredits Continuing Education (CE) programmes for the international medical community.

This program is accredited by the European Board for Accreditation of Continuing Education for Health Professionals (EBAC®) for 15 minutes of effective education time.

EBAC® holds an agreement on mutual recognition of substantive equivalency with the US Accreditation Council for CME (ACCME) and the Royal College of Physicians and Surgeons of Canada, respectively.

Through an agreement between the European Board for Accreditation of Continuing Education for Health Professionals (EBAC®) and the American Medical Association, physicians may convert EBAC® External CME credits to AMA PRA Category 1 Credits. Information on the process to convert EBAC® credit to AMA credit can be found on the AMA website. Other healthcare professionals may obtain from the AMA a certificate of participation in an activity eligible for conversion of credit to AMA PRA Category 1 Credit.

The Accreditation Council for Continuing Medical Education (ACCME) and the Royal College of Physicians and Surgeons of Canada hold an agreement on substantial equivalency of accreditation systems with EBAC.

EBAC® is a member of the International Academy for CPD Accreditation (IACPDA) and a partner member of the International Association of Medical Regulatory Authorities (IAMRA).

System Requirements

Mobile device (e.g., large-format smart phone; laptop or tablet computer) or desktop computer with a video display of at least 1024 × 768 pixels at 24-bit color depth, capable of connecting to the Internet at broadband or faster speeds, with a current version Internet browser and popular document viewing software (e.g., Microsoft Office, PDF viewer, image viewer) installed. Support for streaming or downloadable audio-visual materials (e.g., streaming MP4, MP3 audio) in hardware and software may be required to view, review, or participate in portions of the program.

Unapproved and/or off-label use disclosure

AffinityCE/MedAll requires CE faculty to disclose to the participants:

  • When products or procedures being discussed are off-label, unlabeled, experimental, and/or investigational (not US Food and Drug Administration [FDA] approved); and
  • Any limitations on the information presented, such as data that are preliminary or that represent ongoing research, interim analyses, and/or unsupported opinion.

CME Inquiries

For all CME policy-related inquiries, please contact us at ce@affinityced.com.

Participation Costs

There is no cost to participate in this program.

Requirements for Completion

To receive credit, participants must complete the full activity, the post-test, and the evaluation form before the stated expiration date. There are no prerequisites, and there is no fee to participate or claim credit. A Certificate of Completion will be issued upon successful completion of all required components.

A minimum passing score of 70% on the post-test is required. Participants should consult their own professional licensing authority regarding eligibility to claim credit for this educational activity.

EBAC® only awards CE certificates in increments of 1.0 credit.

Launch and Expiration Date: 2 March 2026 – 20 February 2028

Estimated time to complete this activity: 15 minutes

Disclaimer

This activity is intended for educational purposes only and does not establish a standard of care or replace clinical judgment. Any therapeutic or diagnostic strategies discussed must be evaluated in the context of each patient’s clinical circumstances, risks, and current evidence.

Learners should consult authoritative clinical guidelines and approved product information when considering treatment decisions.

All materials are used with permission. The views expressed are those of the faculty and do not necessarily reflect those of the accredited providers, MedAll, or any supporters.

Content is accurate as of the date of release.

Learning objectives

By the end of this session, participants will be better able to:

  • Differentiate and apply understanding of mechanisms of action of emerging non-chemotherapy agents, including radioligands, antibody-drug conjugates, and immunotherapies, to guide therapy selection.
Claim CME credit

Related content

Similar communities

View all

Similar events and on demand videos

Claim CME credit

Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

For this next session, the learning objective is to differentiate and apply understanding of mechanisms of action of emerging non-chemotherapeutic agents, including novel radioligands, antibody drug conjugates, and novel immunotherapies. So let's begin again with a polling question. Now we have a 62-year-old man with minimally symptomatic metastatic castration resistant prostate cancer. He's been through a lot of primary systemic therapies, starting off with ADT abiraterone, followed by sipulusil T, then docetaxel chemotherapy, then a second RP and zalutamide, and most recently luitian PSMA 617. At the time of presentation, he has minimal bone pain with a pain score of 2 out of 10. A reasonable, although not perfect performance status with a score of one. And unfortunately, he has a growing liver lesion, uh which is biopsied and uh shows adenocarcinoma without uh neuroendocrine or small cell histology. And the immunohistochemistry from the liver biopsy shows high STE one protein expression. Which of these investigational agents targetste one, please cast your vote. So let's review the emerging experimental options for patients with advanced stage disease. Here, we're gonna be focusing on the right-hand side of the diagram for patients that have received many or most of the FDA approved agents for CRPC. We talked already in the previous session about radioligand therapies. These are, uh, radiotherapeutic molecules that are conjugated to ligands, uh, against cell surface proteins such as PSMA, but there are other uh cell surface receptors that can be targeted as well. Uh, we spoke already briefly about the PSMA 4 trial which led to the FDA approval of Letitian PSMA in the pre-chemotherapy space in patients with first-line metastatic CRPC, uh, after one prior RFP therapy. But there have been 2 other agents tested in this space. Um, the first one was tested in the splash study. Um, the radio ligand here is known as Letitia 177 PNT 2002. And uh the third one is the uh eclipse trial uh testing lutetium 177 PSMAINT. So these are all uh PSMA targeting, lutetium 177 delivering radioligands, but uh there are differences here in terms of the, uh, the chelators used and the Linkers and also the ligands. So the ligands are different from the uh PSMA 617. The 2nd and 3rd trials, Slash and eclipse, used the 2 to 1 randomizations as opposed to 1 to 1 used in the PSMA 4 study. And uh notably the splash trial used a dosing regimen that was uh lower, uh, less frequent, and fewer doses than the PSMA 4 regimen. So you can see there. A dose of 6.8 gigabecrels, which is equivalent to 184 milliuries, and that was given once every 8 weeks rather than once every 6 weeks for a total of up to 4 doses rather than up to 6 doses. So keep that in mind when I will show you the results of the splash trial. The eclipse trial. Began with a dose of 7.4 gigab Becrel's 200 milliuries. Uh, every 6 weeks for a total of 4 doses. And during the conduct of the trial, the protocol was modified to increase the number of doses to 6 doses rather than 4. so a proportion of patients on the eclipse trial received 7.4 gigabeels 4 times and another proportion received the same dose 6 times. So the eclipse trial is able to analyze the effect of A number of doses, 4 versus 6, in addition to the Quotes unquote higher dose of uh the radioligand at 7.4 gigaberes. The splash trial results have been reported. Uh, this was a presentation at ESMO 2024. Once again, the trial design was first line MCRPC, one prior RP 2 to 1 randomization against Letitia PSMA PNT 2002 versus Uh RP switch. Again, this trial had a crossover that was built into its design, and 84.6% of patients initially randomized to RP crossed over to the radioligand agent. The radiographic progression free survival endpoint was met, although the hazard ratio was more modest than that seen in the PSMA4 study, and in the overall survival analysis, there was no difference in any direction favoring uh either Letitia PNT 2002 or RP switch. If you compare head to head the RPFS results of PSMA 4, which led to the FDA approval of Letitian PSMA 617 in the pre-chemo space, and the Splash trial, you can see it has a ratio of 0.49 in PSMA4 versus 0.71 in splash. So clearly, um, a diluted effect and as I mentioned before, This is primarily in my mind, due to the reduced dose of the radioligand and the reduced interval 8 weeks instead of 6 weeks, and the lower number of doses being 4 rather than 6. Um, if you look at the PSA responses and the objective responses, you will also note numerically fewer responses in the splash trial relative to the PSMA4 trial. The, um, the Letitia 177 PNT 2002 um will not be um filing for FDA approval, so that agent is not expected to reach the market in the US. The third one, which is the eclipse trial, has been presented only as a press release, and we are expecting to see the top line uh progression free survival and overall survival data at a future congress, but at the moment, all we have is a press release, um, disclosing that the primary RPFS endpoint has been met, but no details or statistics have been given so far. So please keep your eyes open for the uh public presentation of these data at a future congress. I also want to talk about another uh entity uh targeting PSMA, but here, instead of having a ligand that attaches to the PSMA receptor, we have an antibody. So this is called a radio antibody as opposed to a radioligand. It still targets PSMA and it still delivers the TM 177, a beta particle, and The agent is known as letitium 177 rosopatimab extrazein. Uh, this was previously known as Luitium J591, uh, developed by Doctor Neil Bander. The phase 3 trial of this agent is also targeting the first-line metastatic CRPC population in patients who have received one prior ARPI. Uh, docetaxel is only permitted if it was given in the metastatic hormone sensitive setting. And more than 6 months have passed between the final dose of Taxol and randomization. And here, uh, there's a 2 to 1 randomization. Uh, if you cast your eye to the right part of the slide where it says a randomized treatment expansion 490. And the agent here is the radio antibody, uh, 177 Letitia rosopatimab extrazein, and the control arm interestingly here uh allows either the RP switch. Or importantly, uh, docetaxel chemotherapy. So this trial will also have the ability uh to