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Global Perspectives on PARP inhibitor Combinations in mCRPC Match Play: European vs. US Integration in Practice

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  • Overview

    While the development of advanced prostate cancers is largely influenced by androgen receptor (AR) signaling, DNA-damage response (DDR) pathways also contribute to disease progression. AR axis-targeted therapies (ARATs) have been the standard of care for first-line mCRPC. Inhibiting PARP activity is an effective strategy for targeting malignant cells with limited DNA repair capacity due to DDR gene mutations, leading to synthetic lethality. There may be a synergy between ARATs and PARP inhibitors (PARPi), as ARATs can induce HRR deficiencies and PARP inhibitors can increase the activity of ARATs through AR-dependent transcription. Recent clinical trial results have demonstrated that the combination of PARPi with ARATs is safe and effective for the first-line treatment of patients with mCRPC, with 3 combinations now FDA-approved: olaparib + abiraterone, talazoparib + enzalutamide, and niraparib + abiraterone. 

    This activity will provide expert contextualization of evidence from first-line mCRPC clinical trials exploring these combinations, including insights about the differentiation of both treatment and patient selection, as well as management of treatment-related toxicities. Given the differences in approvals and guidelines between the US and European context, this Ryder Cup themed Expert Panel Discussion will compare and contrast the approach in both regions, giving participants comprehensive education on how best to incorporate these combinations into clinical practice. This activity is designed to bring insights presented at major conferences this year to clinicians treating patients with mCRPC, as well as contrast the different global approaches to the disease so clinicians can keep pace with this fast-moving field. 

  • Disclosure of Conflicts of Interest

    Disclosure of Relevant Financial Relationships
    AXIS Medical Education requires faculty, instructors, authors, planners, directors, managers, peer reviewers, and other individuals who are in a position to control the content of this activity to disclose all personal financial relationships they may have in the past 24 months with ineligible companies. An ineligible entity is any organization whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients. All relevant financial relationships are identified and mitigated prior to initiation of the planning phase for an activity. 

    AXIS has mitigated and disclosed to learners all relevant financial relationships disclosed by staff, planners, faculty/authors, peer reviewers, or others in control of content for this activity. Disclosure of a relationship is not intended to suggest or condone bias in any presentation but is made to provide participants with information that might be of potential importance to their evaluation of a presentation or activity. Disclosure information for faculty, authors, course directors, planners, peer reviewers, and/or relevant staff is provided with this activity.

    The faculty reported the following relevant financial relationships or relationships they have with ineligible companies of any amount during the past 24 months:

     Neeraj Agarwal, MD, FASCO, has no real or apparent conflicts of interest to report.

    Elena Castro, MD, PhD, reported a financial interest/relationship or affiliation in the form of Advisor/Consultant; AstraZeneca Pharmaceuticals LP, Bayer HealthCare, Inc., Daiichi-Sankyo, Inc., Janssen Oncology, Lilly, Medscape, Merck & Co., Inc., MSD, Novartis Pharmaceuticals Corporation, Pfizer, Inc. Speaker; AstraZeneca Pharmaceuticals LP, Astellas Pharma US, Inc., Bayer Healthcare, Inc., Janssen Oncology, Novartis Pharmaceuticals Corporation, Pfizer, Inc., Sandoz, Telix. Research grant; Bayer Healthcare, Inc., Janssen Oncology, Pfizer, Inc.

    Neal D. Shore, MD, FACS, reported a financial interest/relationship or affiliation in the form of Consultant; AbbVie, Accord, Alessa Therapeutics, Amgen, Inc., Antev, Arquer, Asieris, Astellas Pharma US, Inc., AstraZeneca Pharmaceuticals LP, Aura Biosciences, Bayer Pharmaceuticals Corporation, Bioprotect, Bristol-Myers Squibb Company, Boston Scientific, Cognology, Clarity, Cold Genesys, Dendreon Corporation, Exact Imaging, Genentech/Roche, Ferring Pharmaceuticals, Inc., Fize Medical, Foundation Medicine, Genesis Care , Immunity Bio, Incyte Corporation, Invitae, Janssen Oncology, Lantheus, Lilly, MDXHealth, Merck & Co., Inc., Minomic, Myovant, Myriad, Nonagen, Novartis Pharmaceuticals Corporation, Nymox, Palette Propella, Sanofi Genzyme, Speciality Networks, Telix, Tolmar Inc., Urogen.

     Axel S. Merseburger, MD reported a financial interest/relationship or affiliation in the form of Advisor/Consultant; Amgen, Inc., Apogepha, Astellas Pharma US, Inc., Bayer Pharmaceuticals Corporation, Bristol-Myers Squibb Company, Clovis Oncology, Ferring Pharmaceuticals, Inc., Hexal, Ipsen Pharmaceuticals, Janssen Oncology, Merck & Co., Inc., MSD, Novartis Pharmaceuticals Corporation, Sanofi, Takeda Oncology, TEVA. Speaker; Amgen, Inc., Apogephia, Astellas Pharma US, Inc., Bayer Pharmaceuticals Corporation, Bristol-Myers Squibb Company, Clovis Oncology, Ferring Pharmaceuticals, Inc., Hexel, Ipsen Pharmaceuticals, Janssen, Merck & Co., Inc., MSD, Novartis Pharmaceuticals Corporation, Roche, Sanofi, Takeda Oncology, TEVA.

    The directors, planners, managers, peer reviewers, and relevant staff reported the following financial relationships they have with any ineligible company of any amount during the past 24 months:  Linda Gracie-King, MS; Jocelyn Timko, BS; Marilyn L. Haas-Haseman, PhD, RN, CNS, ANP-BC; Adrienne N. Nedved, MPA, PharmD, BCOP; Melissa Duffy, PA-C; and Dee Morgillo, MEd, MT(ASCP), CHCP hereby state that they do not have any financial relationships or relationships any ineligible company of any amount during the past 24 months.  Robert Geist, MD, reported a financial interest/relationship or affiliation during the past 24 months as a past employee of Fresenius Medical Care. Robert Mocharnuk, MD, reported a financial interest/relationship or affiliation in the form of Common stock: Merck of any amount during the past 24 months. 

  • Learning Objectives

    At the conclusion of this activity, participants should be better able to:

    • Identify the biological and clinical rationale for PARP inhibitor combinations as potential treatments in patients with mCRPC
    • Integrate clinical trial evidence to inform potential future treatment strategies with PARPi combinations in the frontline setting of mCRPC
    • Differentiate PARPi combinations in frontline mCRPC by efficacy, safety and patient-reported outcomes
    • Identify mCRPC patient populations likely to benefit from PARP- and AR-inhibitor combinations based on clinical trial evidence
  • Target Audience

    This educational activity is designed for European and US medical oncologists, urologists, pathologists/lab professionals, oncology nurses, nurse practitioners, physician assistants, and other healthcare professionals who are part of the interprofessional team responsible for the therapeutic management of patients with prostate cancer.

  • Accreditation and Credit Designation Statements

    Accreditation Statement

    In support of improving patient care, AXIS Medical Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. 

     This activity was planned by and for the healthcare team, and learners will receive 0.75 Interprofessional Continuing Education (IPCE) credit for learning and change. 

    Credit Designation for Physicians
    AXIS Medical Education designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credit(s)™.  Physicians should claim only the credit commensurate with theextent of their participation in the activity.

    Credit Designation for Physician Assistants

    AXIS Medical Education has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.75 AAPA Category 1 CME credits.  Approval is valid until 12/20/2024 PAs should only claim credit commensurate with the extent of their participation.

     Credit Designation for Pharmacists
    This knowledge-based activity is approved for 0.75 contact hour of continuing pharmacy education JA4008106-0000-23-054-H01-P.

    Credit Designation for Nursing
    AXIS Medical Education designates this continuing nursing education activity for 0.75 contact hour.

    Learners are advised that accredited status does not imply endorsement by the provider or ANCC of any commercial products displayed in conjunction with an activity.

     Credit Designation for Laboratory Professionals
    This continuing medical laboratory education activity is recognized by the American Society for Clinical Pathology as meeting the criteria for 0.75 CMLE credit. ASCP CMLE credits are acceptable to meet the continuing education requirement for the ASCP Board of Registry Certification Maintenance Program.

  • Provider(s)/Educational Partner(s)

    Provided by

     

  • Commercial Support

    This activity is supported by an educational grant from Pfizer Inc.

  • Disclaimer

    Disclosure of Unlabeled Use                         
    This educational activity may contain discussion of agents that are not approved for use by the FDA and/or investigational (“off-label”) uses of agents that are approved by the FDA. The planners of this activity do not recommend the use of any agent outside of its labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each agent for information on its approved indications, contraindications, warnings, and other, related information.

     Disclaimer       
    Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures,

    medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

  • Publication Dates

    Release Date:

    Expiration Date:

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Details
Presenters
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Comments
  • Overview

    While the development of advanced prostate cancers is largely influenced by androgen receptor (AR) signaling, DNA-damage response (DDR) pathways also contribute to disease progression. AR axis-targeted therapies (ARATs) have been the standard of care for first-line mCRPC. Inhibiting PARP activity is an effective strategy for targeting malignant cells with limited DNA repair capacity due to DDR gene mutations, leading to synthetic lethality. There may be a synergy between ARATs and PARP inhibitors (PARPi), as ARATs can induce HRR deficiencies and PARP inhibitors can increase the activity of ARATs through AR-dependent transcription. Recent clinical trial results have demonstrated that the combination of PARPi with ARATs is safe and effective for the first-line treatment of patients with mCRPC, with 3 combinations now FDA-approved: olaparib + abiraterone, talazoparib + enzalutamide, and niraparib + abiraterone. 

    This activity will provide expert contextualization of evidence from first-line mCRPC clinical trials exploring these combinations, including insights about the differentiation of both treatment and patient selection, as well as management of treatment-related toxicities. Given the differences in approvals and guidelines between the US and European context, this Ryder Cup themed Expert Panel Discussion will compare and contrast the approach in both regions, giving participants comprehensive education on how best to incorporate these combinations into clinical practice. This activity is designed to bring insights presented at major conferences this year to clinicians treating patients with mCRPC, as well as contrast the different global approaches to the disease so clinicians can keep pace with this fast-moving field. 

  • Disclosure of Conflicts of Interest

    Disclosure of Relevant Financial Relationships
    AXIS Medical Education requires faculty, instructors, authors, planners, directors, managers, peer reviewers, and other individuals who are in a position to control the content of this activity to disclose all personal financial relationships they may have in the past 24 months with ineligible companies. An ineligible entity is any organization whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients. All relevant financial relationships are identified and mitigated prior to initiation of the planning phase for an activity. 

    AXIS has mitigated and disclosed to learners all relevant financial relationships disclosed by staff, planners, faculty/authors, peer reviewers, or others in control of content for this activity. Disclosure of a relationship is not intended to suggest or condone bias in any presentation but is made to provide participants with information that might be of potential importance to their evaluation of a presentation or activity. Disclosure information for faculty, authors, course directors, planners, peer reviewers, and/or relevant staff is provided with this activity.

    The faculty reported the following relevant financial relationships or relationships they have with ineligible companies of any amount during the past 24 months:

     Neeraj Agarwal, MD, FASCO, has no real or apparent conflicts of interest to report.

    Elena Castro, MD, PhD, reported a financial interest/relationship or affiliation in the form of Advisor/Consultant; AstraZeneca Pharmaceuticals LP, Bayer HealthCare, Inc., Daiichi-Sankyo, Inc., Janssen Oncology, Lilly, Medscape, Merck & Co., Inc., MSD, Novartis Pharmaceuticals Corporation, Pfizer, Inc. Speaker; AstraZeneca Pharmaceuticals LP, Astellas Pharma US, Inc., Bayer Healthcare, Inc., Janssen Oncology, Novartis Pharmaceuticals Corporation, Pfizer, Inc., Sandoz, Telix. Research grant; Bayer Healthcare, Inc., Janssen Oncology, Pfizer, Inc.

    Neal D. Shore, MD, FACS, reported a financial interest/relationship or affiliation in the form of Consultant; AbbVie, Accord, Alessa Therapeutics, Amgen, Inc., Antev, Arquer, Asieris, Astellas Pharma US, Inc., AstraZeneca Pharmaceuticals LP, Aura Biosciences, Bayer Pharmaceuticals Corporation, Bioprotect, Bristol-Myers Squibb Company, Boston Scientific, Cognology, Clarity, Cold Genesys, Dendreon Corporation, Exact Imaging, Genentech/Roche, Ferring Pharmaceuticals, Inc., Fize Medical, Foundation Medicine, Genesis Care , Immunity Bio, Incyte Corporation, Invitae, Janssen Oncology, Lantheus, Lilly, MDXHealth, Merck & Co., Inc., Minomic, Myovant, Myriad, Nonagen, Novartis Pharmaceuticals Corporation, Nymox, Palette Propella, Sanofi Genzyme, Speciality Networks, Telix, Tolmar Inc., Urogen.

     Axel S. Merseburger, MD reported a financial interest/relationship or affiliation in the form of Advisor/Consultant; Amgen, Inc., Apogepha, Astellas Pharma US, Inc., Bayer Pharmaceuticals Corporation, Bristol-Myers Squibb Company, Clovis Oncology, Ferring Pharmaceuticals, Inc., Hexal, Ipsen Pharmaceuticals, Janssen Oncology, Merck & Co., Inc., MSD, Novartis Pharmaceuticals Corporation, Sanofi, Takeda Oncology, TEVA. Speaker; Amgen, Inc., Apogephia, Astellas Pharma US, Inc., Bayer Pharmaceuticals Corporation, Bristol-Myers Squibb Company, Clovis Oncology, Ferring Pharmaceuticals, Inc., Hexel, Ipsen Pharmaceuticals, Janssen, Merck & Co., Inc., MSD, Novartis Pharmaceuticals Corporation, Roche, Sanofi, Takeda Oncology, TEVA.

    The directors, planners, managers, peer reviewers, and relevant staff reported the following financial relationships they have with any ineligible company of any amount during the past 24 months:  Linda Gracie-King, MS; Jocelyn Timko, BS; Marilyn L. Haas-Haseman, PhD, RN, CNS, ANP-BC; Adrienne N. Nedved, MPA, PharmD, BCOP; Melissa Duffy, PA-C; and Dee Morgillo, MEd, MT(ASCP), CHCP hereby state that they do not have any financial relationships or relationships any ineligible company of any amount during the past 24 months.  Robert Geist, MD, reported a financial interest/relationship or affiliation during the past 24 months as a past employee of Fresenius Medical Care. Robert Mocharnuk, MD, reported a financial interest/relationship or affiliation in the form of Common stock: Merck of any amount during the past 24 months. 

  • Learning Objectives

    At the conclusion of this activity, participants should be better able to:

    • Identify the biological and clinical rationale for PARP inhibitor combinations as potential treatments in patients with mCRPC
    • Integrate clinical trial evidence to inform potential future treatment strategies with PARPi combinations in the frontline setting of mCRPC
    • Differentiate PARPi combinations in frontline mCRPC by efficacy, safety and patient-reported outcomes
    • Identify mCRPC patient populations likely to benefit from PARP- and AR-inhibitor combinations based on clinical trial evidence
  • Target Audience

    This educational activity is designed for European and US medical oncologists, urologists, pathologists/lab professionals, oncology nurses, nurse practitioners, physician assistants, and other healthcare professionals who are part of the interprofessional team responsible for the therapeutic management of patients with prostate cancer.

  • Accreditation and Credit Designation Statements

    Accreditation Statement

    In support of improving patient care, AXIS Medical Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. 

     This activity was planned by and for the healthcare team, and learners will receive 0.75 Interprofessional Continuing Education (IPCE) credit for learning and change. 

    Credit Designation for Physicians
    AXIS Medical Education designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credit(s)™.  Physicians should claim only the credit commensurate with theextent of their participation in the activity.

    Credit Designation for Physician Assistants

    AXIS Medical Education has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.75 AAPA Category 1 CME credits.  Approval is valid until 12/20/2024 PAs should only claim credit commensurate with the extent of their participation.

     Credit Designation for Pharmacists
    This knowledge-based activity is approved for 0.75 contact hour of continuing pharmacy education JA4008106-0000-23-054-H01-P.

    Credit Designation for Nursing
    AXIS Medical Education designates this continuing nursing education activity for 0.75 contact hour.

    Learners are advised that accredited status does not imply endorsement by the provider or ANCC of any commercial products displayed in conjunction with an activity.

     Credit Designation for Laboratory Professionals
    This continuing medical laboratory education activity is recognized by the American Society for Clinical Pathology as meeting the criteria for 0.75 CMLE credit. ASCP CMLE credits are acceptable to meet the continuing education requirement for the ASCP Board of Registry Certification Maintenance Program.

  • Provider(s)/Educational Partner(s)

    Provided by

     

  • Commercial Support

    This activity is supported by an educational grant from Pfizer Inc.

  • Disclaimer

    Disclosure of Unlabeled Use                         
    This educational activity may contain discussion of agents that are not approved for use by the FDA and/or investigational (“off-label”) uses of agents that are approved by the FDA. The planners of this activity do not recommend the use of any agent outside of its labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each agent for information on its approved indications, contraindications, warnings, and other, related information.

     Disclaimer       
    Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures,

    medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

  • Publication Dates

    Release Date:

    Expiration Date:

Facebook Comments

Schedule3 Mar 2024