touchTALKS

Improving outcomes in prostate cancer: What is the role of PARP-inhibitor combination therapy?

Access to this content is not permitted for healthcare professionals based in the US.

Back to CME
Prostate Cancer CME ACCREDITED Watch Time: 32 mins

touchTALKS Improving outcomes in prostate cancer: What is the role of PARP-inhibitor combination therapy?

Watch Dr Neal Shore discuss the use of PARP inhibitors for patients with mCRPC and consider their potential as combination treatment with androgen deprivation therapy.

 
Video Chapter
PARP inhibitors for prostate cancer: A deep dive into the evidence

Dr Neal Shore discusses the rationale and the evidence for using PARP inhibitors in metastatic castration-resistant prostate cancer.

view bio and disclosures
1/3 Next Chapter
 
Video Chapter
Clinical strategies in patient selection for PARP inhibitor therapy

Dr Neal Shore discusses germline and somatic mutation testing in mCRPC and factors affecting PARP inhibitor selection in clinical practice.

view bio and disclosures
2/3 Next Chapter
 
Video Chapter
New and emerging PARP inhibitor combinations for prostate cancer

Dr Neal Shore discusses the potential of combining PARP inhibitors with other agents in the management of mCRPC, synthetic lethality with androgen deprivation therapy, and ongoing clinical trials.

view bio and disclosures
3/3 Take CME Test
Take CME Test
Overview & Learning Objectives
Overview

In this activity, Dr Shore will discuss the rationale and evidence for using PARP inhibitors in metastatic castration-resistant prostate cancer, using PARPis in clinical practice, and how PARPis in combination with androgen deprivation therapy are being assessed. read more

Target Audience

This activity has been designed to meet the educational needs of medical oncologists and urologists involved in the management of metastatic castration-resistant prostate cancer.

Potential Conflicts of Interest

USF Health adheres to The Standards for Integrity and Independence in Accredited Continuing Education in all of its continuing professional development activities. It is USF Health’s policy that all persons in a position to influence content in this activity disclose any financial relationship with an ineligible organization. USF Health has mitigated all conflicts of interest.

Faculty

Dr Neal Shore discloses: Consultation/advisory role fees from AbbVie, Ambry, Amgen, Astellas, AstraZeneca, Bayer, , Boston Scientific, Bristol Myers Squibb, Clovis Oncology, Dendreon, Exact Imaging, FerGene, Ferring, Foundation Med, Invitae, Janssen, MDxHealth, Merck, Myovant, Myriad, Nymox, Pfifer, Sanofi Genzyme, and Tolmar; Speaker fees from Astellas, Bayer, Clovic, Janssen, and Pfizer.

Content Reviewer

Jad Chahoud, M.D, M.P.H has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Alison Scott has 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 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 0.5 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The 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)

Learning Objectives

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

  • Discuss the use of combination PARP-inhibitor targeted therapy in the management of prostate cancer
  • Evaluate how to select/identify patients for potential combination PARPi and androgen receptor targeted therapy for prostate cancer
  • Review ongoing clinical trials exploring combination PARPi and androgen-receptor targeted therapy for prostate cancer
Faculty & Disclosures
Dr Neal Shore

Carolina Urologic Research Center, South Carolina, USA

Neal Shore, MD, FACS is the Medical Director for the Carolina Urologic Research Center. He practices with Atlantic Urology Clinics in Myrtle Beach, South Carolina. A graduate of Duke University and Duke University Medical School, Dr Shore completed a 6-month clinical research fellowship in Pretoria, South Africa, and then completed his general surgery/urology training at New York Hospital Cornell Medical Center and at Memorial Sloan Kettering Cancer Center in New York City. He is a Fellow of the American College of Surgeons. read more

Dr Shore has conducted more than 350 clinical trials, focusing mainly on genitourinary (GU) Oncology, and serves on the Boards of Duke Global Health Institute, the Society of Urologic Oncology, and the Bladder Cancer Advocacy Network, and is Immediate Past President of the Large Urology Group Practice Association. He is a founder for both the CUSP Clinical Trials Consortium and DASHKO, large urology practices data registries. He serves as the National Urology Research Director for 21st Century Oncology. He is the Co-Chair of the AUA International Prostate Cancer Forum and has served on the AUA Male Health and AUA Data Committees, the SITC Task Force for Prostate Cancer and Bladder Cancer, and the Bladder Cancer Advocacy Think Tank. He is a member of the Editorial Boards for Reviews in Urology, Urology Times, Chemotherapy Advisor, OncLive, PLOS ONE (Academic Editor), Urology Practice, and World Journal of Urology, and serves as Editor for Everyday Urology Oncology. He has more than 200 peer-reviewed publications and numerous book chapters.

Dr Neal Shore discloses: Consultation/advisory role fees from AbbVie, Ambry, Amgen, Astellas, AstraZeneca, Bayer, , Boston Scientific, Bristol Myers Squibb, Clovis Oncology, Dendreon, Exact Imaging, FerGene, Ferring, Foundation Med, Invitae, Janssen, MDxHealth, Merck, Myovant, Myriad, Nymox, Pfifer, Sanofi Genzyme, and Tolmar; Speaker fees from Astellas, Bayer, Clovic, Janssen, and Pfizer.

Downloads

View and download resources from this activity to support your learning or share with colleagues.

Register to touchONCOLOGY for FREE
  • Peer-reviewed journals and expert opinion.
  • Interactive CME and e-learning modules.
  • Video conference highlights.
Register For Free Now

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

Accept Decline
CME Test (0.5 Points) Close
CME Test

To obtain the CME credit(s), please complete this post-test. Please complete and click to see your results and continue.

Question 1/5
What is the prevalence of HRR gene mutations, including BRCA1, BRCA2, or ATM genes, in men with mCRPC?
Correct

Depending on the study population, it is estimated that between 23 and 33% of men with mCRPC have mutations in the HRR genes, including BRCA1, BRCA2, or ATM genes.1–3

Abbreviations
HRR, homologous recombination repair; mCRPC, metastatic castration-resistant prostate cancer.

References
Lang SH, et al. Int J Clin Oncol. 2019;55:597–616.
Mateo, J, et al. N Engl J Med. 2015; 373:1697–708.

Question 2/5
Your patient is receiving rucaparib for mCRPC. Which of the following adverse events is he most likely to experience?
Correct

In a phase II study, the most common adverse events (all-grade) associated with rucaparib in patients with mCRPC were fatigue or asthenia (61.7%), nausea (52.2%), and anaemia (43.5%). Seizures, skin reactions, haemoptysis, and haematuria are not commonly associated with PARPis. Petechiae are a sign of thrombocytopenia, which is a common adverse effect of PARPis.

Abbreviations
PARPi, poly (ADP-ribose) polymerase inhibitor.

References
Abida W, et al. J Clin Oncol. 2020;38:3763–72.

Question 3/5
Your patient is receiving ADT for mCRPC, but experiences disease progression. There is no family history of BRCA-mutated cancer. What do you do next?
Correct

Initiation of PARPi therapy requires a positive biopsy for HRR mutations.1 Family history of BRCA-mutated cancers (breast, ovarian, prostate cancer, or melanoma) is not always reliable as a decision tool for genetic testing.2

If genetic testing indicates presence of a BRCA1 or BRCA2 mutation, the patient can start either olaparib or rucaparib therapy, in line with current NCCN guidelines.1

Abbreviations
ADT, androgen deprivation therapy; HRR, homologous recombination repair; NCCN, National Comprehensive Cancer Network; PARPi, poly (ADP-ribose) polymerase inhibitor.

References
1. NCCN Guidelines version 1.2021. Available at: www.nccn.org/professionals/physician_gls/pdf/prostate.pdf (accessed 11 March 2021).
2. Cheng H, et al. Am Soc Clin Oncol Educ Book. 2018;38:372–81.

Question 4/5
Your patient with mCRPC is being treated with an ADT, but has rising PSA and ALP levels and is experiencing disease progression. You decide to test them for HRR mutations, as you are considering initiating treatment with PARPi. What do you do next?
Correct

Initiation of PARPi therapy requires a positive test for HRR mutations.1
Both germline and somatic testing are available to identify potential candidates for PARPi therapy. If genetic testing indicates the presence of a BRCA1 or BRCA2 mutation, the patient can start either olaparib or rucaparib therapy, in line with current NCCN guidelines.1

Abbreviations
HRR, homologous recombination repair; NCCN, National Comprehensive Cancer Network; PARPi, poly (ADP-ribose) polymerase inhibitor.

References
NCCN Guidelines version 1.2021. Available at: www.nccn.org/professionals/physician_gls/pdf/prostate.pdf (accessed 11 March 2021).

Question 5/5
What is the rationale for combining an AR blocker with a PARPi for patients with mCRPC?
Correct

Novel hormonal agents are thought to induce an HRR phenotype, which allows patients without an inherent HRR deficiency to benefit from PARP inhibition.1
PARP1 is required for androgen receptor transcriptional activity and for prostate tumour cell growth, generation, and maintenance of castration resistance. Therefore, dual functions of PARP1 in HRR and transcription factor regulation can be leveraged to suppress pathways critical for pre-malignant phenotypes in prostate cancer cells by modulation of the HRR and hormone signalling pathways.1
Androgen receptor signalling has been reported to regulate DNA repair processes in prostate cancer and following androgen deprivation therapy, PARP-mediated repair pathways have been reported to be upregulated in prostate cancers.1

Abbreviations

ADT, androgen deprivation therapy; HRR, homologous recombination repair; PARP, poly (ADP-ribose) polymerase.

References

Antonarakis ES, et al. Eur Urol Oncol. 2020;3:594–611.

Post Test Feedback Close
Step 1: Post CME Test Feedback

Please note this feedback form is compulsory to complete your CME evaluation

Please complete this short online feedback form.
Please indicate how well each statement met your expectations.

Accreditation Close
Accreditation

Please provide your details so that we can send you your certificate, which will be emailed to the address provided. All fields are required.

Your Accreditation Close
Copied to clipboard!
accredited arrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-whiteticktimetranscriptup-arrowwebinar Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72