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Prostate Cancer CE/CME ACCREDITED Watch Time: 32 mins

touchMDT PARP inhibitors in prostate cancer: New combinations, new possibilities

Watch leading specialists discuss new PARP inhibitor combinations for the treatment of advanced prostate cancer

 Overview & Learning Objectives

Patient with advanced prostate cancer
Oncology Pharmacist and Medical Oncologist
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PARP inhibitor combinations: Rationale Dr Holle, Dr Abida

Watch an oncology pharmacist and medical oncologist discuss the rationale for PARP inhibitor combinations in the treatment of advanced prostate cancer.

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Urologist and Medical Oncologist
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PARP inhibitor combination trials Prof. Merseburger, Dr Abida

Watch a urologist and a medical oncologist discuss PARP inhibitor combination clinical trials, including recent data.

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Medical Oncologist, Urologist and Oncology Pharmacist
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Extending benefit of PARP inhibitors Dr Abida, Prof. Merseburger, Dr Holle

Watch a medical oncologist, urologist and oncology pharmacist share their expert insights on extending the benefit of PARP inhibitors through combinations.

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Oncology Pharmacist and Medical Oncologist

Watch an oncology pharmacist and medical oncologist discuss the rationale for PARP inhibitor combinations in the treatment of advanced prostate cancer.
Expert Spotlight
Dr Lisa Holle
University of Connecticut School of Pharmacy, Storrs, and UConn Health: Neag Comprehensive Cancer Center, Farmington, CT, USA
Dr Wassim Abida
Memorial Sloan Kettering Cancer Center, New York City, NY, USA

Dr Lisa Holle and Dr Wassim Abida discuss the rationale for PARP inhibitor combinations in the treatment of advanced prostate cancer.

Listen on the Go

 Learn more Back to MDT Hub Time: 11:08
 
Urologist and Medical Oncologist

Watch a urologist and a medical oncologist discuss PARP inhibitor combination clinical trials, including recent data.
Expert Spotlight
Prof. Axel Merseburger
University Hospital Schleswig-Holstein, Lübeck, Germany
Dr Wassim Abida
Memorial Sloan Kettering Cancer Center, New York City, NY, USA

Prof. Axel Merseburger and Dr Wassim Abida discuss PARP inhibitor combination clinical trials.

Listen on the Go

 Learn more Back to MDT Hub Time: 10:46
 
Medical Oncologist, Urologist and Oncology Pharmacist

Watch a medical oncologist, urologist and oncology pharmacist share their expert insights on extending the benefit of PARP inhibitors through combinations.
Expert Spotlight
Dr Wassim Abida
Memorial Sloan Kettering Cancer Center, New York City, NY, USA
Prof. Axel Merseburger
University Hospital Schleswig-Holstein, Lübeck, Germany
Dr Lisa Holle
University of Connecticut School of Pharmacy, Storrs, and UConn Health: Neag Comprehensive Cancer Center, Farmington, CT, USA

Dr Wassim Abida, Prof. Axel Merseburger and Dr Lisa Holle discuss extending the benefit of PARP inhibitors through combinations.

Listen on the Go

 Learn more Back to MDT Hub Time: 10:38
 
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Learning Objectives & Overview
Overview

In this activity, specialists in the MDT involved in caring for patients with advanced prostate cancer share their perspectives on PARP inhibitor combinations, including the rationale for their use, recent clinical trial data and extending the benefit of PARP inhibitor combinations.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of oncologists, urologists, prostate cancer specialists, oncology nurses and hospital pharmacists involved in the management of patients with advanced prostate cancer globally, with a focus on the USA.

All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty 

Dr Wassim Abida discloses: Advisory board or panel fees from AstraZeneca/MedImmune, Clovis Oncology, Daiichi Sankyo, Janssen and ORIC Pharmaceuticals. Consultant fees from Aptitude Health and Roche. Grants/research support from AstraZeneca, Clovis Oncology, Epizyme, ORIC Pharmaceuticals and Zenith Epigenetics.

Prof. Axel Merseburger discloses: Advisory board or panel fees from Astellas, AstraZeneca, Clovis Oncology, Exelixis, Ipsen, Janssen and Roche. Speaker’s bureau fees from Astellas, AstraZeneca, Clovis Oncology, Exelexis, Ipsen, Janssen and Roche.

Dr Lisa Holle has no financial interests/relationships or affiliations in relation to this activity.

Content reviewer

Alicia Ann Canalejo has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Katrina Lester and Christina Mackins-Crabtree have no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

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 a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Pharmacists

USF Health is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This knowledge-based program has been approved for 0.75 contact hours (0.75 CEUs). Universal program number is as follows: 0230-0000-22-004-H01-P.

This activity can be viewed on any web browser such as, but not limited to, Google Chrome, Firefox, Safari, Opera, Microsoft Edge and Internet Explorer.

Nurses

USF Health is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation.

A maximum of 0.75 contact hours may be earned by learners who successfully complete this continuing professional development activity. USF Health, the accredited provider, acknowledges touchIME as the joint provider in the planning and execution of this CNE activity.

This activity is awarded 0.75 ANCC pharmacotherapeutic contact hour.

Date of original release: 5 May 2022. Date credits expire: 5 May 2023.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

Learning Objectives

After watching this activity, participants should be better able to:

  • Analyse the mechanism of action of PARP inhibitors and the biological and clinical rationale for PARP inhibitor combinations in the treatment of advanced prostate cancer
  • Discuss key data from clinical trials with PARP inhibitor combinations in the management of advanced prostate cancer
  • Recognize the potential for extended benefit of PARP inhibitor combinations in advanced prostate cancer beyond HRR gene mutations
Faculty & Disclosures
Dr Wassim Abida

Memorial Sloan Kettering Cancer Center, New York City, NY, USA

Dr Wassim Abida is a Clinical and Translational Investigator at the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center, NY, USA. read more

His research focuses on the genomics and epigenetics of prostate cancer and on the development of molecular-guided therapies in prostate cancer and other solid tumours. Dr Abida has served as the global lead on several studies targeting DNA repair, including a study that led to the first FDA approval of a PARP inhibitor for prostate cancer. 

Dr Abida’s awards include a Department of Defense Physician Research Award, a Young Investigator Award and a Challenge Award from the Prostate Cancer Foundation, as well as Merit Awards from the Conquer Cancer Foundation of American Society of Clinical Oncology (ASCO).

Dr Wassim Abida discloses: Advisory board or panel fees from AstraZeneca/MedImmune, Clovis Oncology, Daiichi Sankyo, Janssen and ORIC Pharmaceuticals. Consultant fees from Aptitude Health and Roche. Grants/research support from AstraZeneca, Clovis Oncology, Epizyme, ORIC Pharmaceuticals and Zenith Epigenetics.
Prof. Axel Merseburger

University Hospital Schleswig-Holstein, Lübeck, Germany

Prof. Axel Merseburger is Professor of Urology and Chairman of the Department of Urology at University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. read more

Prof. Merseburger is trained in all aspects of open and endoscopic urology and has a specific interest in laparoscopic and robotic-assisted surgery, particularly for the management of prostate, renal and bladder cancer. His research activity encompasses both molecular and clinical aspects of uro-oncology, focusing on biomarkers and prognostic factors for prostate cancer, renal cell carcinoma and transitional cell carcinoma. Prof. Merseburger is principal investigator in multiple phase II and III uro-oncology clinical trials.


Prof. Merseburger is a member of various uro-oncology organizations; he is chairman of the European Scholarship Programme (ESUP) the European Association of Urology (EAU), and was the chairman of the EAU Guideline Group for Lasers and Technologies.

Prof. Merseburger is a reviewer and editorial board member for several urology and oncology journals, and serves as associate editor of the World Journal of Urology and editor-in-chief of the European Journal of Haematology and Oncology and Aktuelle Urologie. He has published widely in the field, having authored or co-authored over 300 peer-reviewed articles.

Prof. Axel Merseburger discloses: Advisory board or panel fees from Astellas, AstraZeneca, Clovis Oncology, Exelixis, Ipsen, Janssen and Roche. Speaker’s bureau fees from Astellas, AstraZeneca, Clovis Oncology, Exelexis, Ipsen, Janssen and Roche.
Dr Lisa Holle

University of Connecticut School of Pharmacy, Storrs, and UConn Health: Neag Comprehensive Cancer Center, Farmington, CT, USA

Dr Holle is a Clinical Professor at the UConn School of Pharmacy and at the UConn School of Medicine, CT, USA. Her practice site is at the UConn Health: Neag Comprehensive Cancer Center, where she works in a team-based ambulatory care clinic focusing on genitourinary and gastrointestinal cancers. read more

Dr Holle has worked as an oncology pharmacist for over 20 years in a variety of settings, including private hospitals, academic medical centres and medical communications. 

Dr Holle is a past president of the Hematology Oncology Pharmacy Association (HOPA), and a past secretariat member and past treasurer of the International Society of Oncology Pharmacy Practitioners (ISOPP). She is also an active member in many other professional oncology and pharmacy organizations. 

Dr Holle’s clinical research programme focuses on numeracy and patient decision making, oncology quality improvement initiatives, medical marijuana and oral anticancer therapy management. She has authored numerous articles and chapters on oncology and teaching-related topics.

Dr Lisa Holle has no financial interests/relationships or affiliations in relation to this activity.
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This Activity Is Funded By:

An independent medical education grant from Pfizer.
This activity is jointly provided by USF Health and touchIME.

The information provided by this CE activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CE to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

This content is intended for healthcare professionals.

Date of original release: 5 May 2022. Date credits expire: 5 May 2023.

This content is intended for healthcare professionals only. Please confirm that you are a healthcare professional.

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Question 1/5
Which of the following statements best describes the concept of synthetic lethality specific to tumour cells?

HR, homologous recombination; HRR, homologous recombination repair; PARP, poly(ADP-ribose) polymerase.
 Correct

PARP inhibition prevents PARylation, the process by which PARP enzymes catalyse the repair of DNA single-stranded breaks. Unrepaired single-stranded breaks are converted into double-stranded breaks during tumour cell replication. In HR-deficient tumour cells, this process of PARP inhibition induces a synergistic lethal effect, increasing genomic instability enough to reach tumour cell death. This phenomenon is called synthetic lethality and is specific to tumour cells with complete HR deficiency.

Abbreviations

HR, homologous recombination deficient; PARP, poly(ADP-ribose) polymerase.

Reference

Teyssonneau D, et al. J Hematol Oncol. 2021;14:51.

Question 2/5
Your patient is a 69-year-old male with mCRPC. He has previously received docetaxel and enzalutamide treatment, and genetic testing has shown the presence of a germline BRCA2 mutation. He is being considered for a clinical trial investigating a next-generation AR inhibitor in combination with a PARP inhibitor. How would you best describe the rationale for this treatment combination?

ADT, androgen deprivation therapy; AR, androgen receptor; HR, homologous recombination; HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer; PARP, poly(ADP-ribose) polymerase.
 Correct

AR inhibition results in downregulation of HRR genes in some preclinical models and may sensitize prostate cancer cells to PARP inhibition.1–3

Abbreviations

AR, androgen receptor; HRR, homologous recombination repair; PARP, poly(ADP-ribose) polymerase.

References

  1. Polkinghorn WR, et al. Cancer Discov. 2013;3:1245–53.
  2. Teyssonneau D, et al. J Hematol Oncol. 2021;14:51.
  3. Li L, et al. Sci Signal. 2017;10:eaam7479.
Question 3/5
The phase III MAGNITUDE and PROpel studies are investigating first-line combinatorial treatment of niraparib and abiraterone, and olaparib and abiraterone, respectively, in patients with mCRPC. What is the primary endpoint of these trials?

mCRPC, metastatic castration-resistant prostate cancer.
 Correct

The primary endpoint of both trials, MAGNITUDE and PROpel, is radiographic progression-free survival, by central review and investigator assessment, respectively. Overall survival and overall/objective response rate are secondary endpoints in both trials, and time to prostate-specific antigen progression is a secondary endpoint in MAGNITUDE.1,2

Abbreviation

mCRPC, metastatic castration-resistant prostate cancer.

References

  1. Chi KM, et al. J Clin Oncol. 2022;40(Suppl. 6):12.
  2. Saad F, et al. J Clin Oncol. 2022;40(Suppl. 6):11.
Question 4/5
Your patient has mCRPC without HRR mutations, and you wish to discuss the option of enrolling them in a PARP inhibitor combination trial. Clinical data from which of the following PARP inhibitor combination trials would guide your discussion and recommendation, in terms of eligibility for available trials?

HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer; PARP, poly(ADP-ribose) polymerase.
 Correct

PROpel is a phase III trial investigating first-line combination treatment with olaparib and abiraterone in patients with mCRPC, with and without HRR gene mutations. Interim data from 796 patients, presented at the 2022 ASCO Genitourinary Cancers Symposium, showed that the study had already met its primary endpoint of investigator-assessed rPFS, and rPFS improvement was recorded in patients with HRR mutations. The safety and tolerability profile of the combination was consistent with the known safety profiles of the individual drugs.1 

CASPAR (NCT04455750), the TRAP Trial (NCT03787680) and COMRADE (NCT03317392) are ongoing PARP inhibitor combination trials in patients with mCRPC that are yet to report data.2,3 CASPAR is a phase III trial that includes patients with and without BRCA1, BRCA2 or PALB2 gene mutations.3

Abbreviations

ASCO, American Society of Clinical Oncology; HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer; PARP, poly(ADP-ribose) polymerase; rPFS, radiographic progression-free survival.

References

  1. Saad F, et al. J Clin Oncol. 2022;40(Suppl. 6):11.
  2. Trial information listed by NCT identifier at ClinicalTrials.gov (accessed 6 April 2022).
  3. Rao A, et al. J Clin Oncol. 2019;37(Suppl. 6):TPS181.
Question 5/5
Your 68-year-old male patient has recently been diagnosed with mCRPC and is mildly symptomatic. He has an ECOG performance status of 1 and a Gleason score at diagnosis of 9. With evidence-based guidelines in mind, which of the following next steps would you consider?

ECOG, Eastern Cooperative Oncology Group; mCRPC, metastatic castration-resistant prostate cancer.
 Correct

The National Comprehensive Cancer Network 2022 guidelines recommend germline and/or somatic homologous recombination repair gene panel and BRCA testing to identify pathogenic mutations to inform treatment decisions.

The PARP inhibitor olaparib is a recommended treatment for patients with mCRPC and a germline or somatic mutation in a homologous recombination repair gene (e.g. BRCA1 or BRCA2) who have been previously treated with receptor-directed androgen deprivation therapy.

Abbreviations

mCRPC, metastatic castration-resistant prostate cancer; PARP, poly(ADP-ribose) polymerase.

Reference

NCCN Prostate Cancer Version: 3.2022. 2022. Available at: www.nccn.org/professionals/physician_gls/pdf/prostate.pdf (accessed 3 March 2022).

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