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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 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Clovis Oncology, Inc.

Medical Crossfire®: Defining New Roles for the Application of PARP Inhibition Strategies in Multiple Tumor Types

Release Date: December 31, 2017
Expiration Date: December 31, 2018
Media: Internet - based

 

Activity Overview

This online activity features an expert panel discussion of current and emerging roles for PARP inhibitors in the management of patients with ovarian, breast, and prostate cancer. Our panel of experts will use the growing foundation of clinical evidence pertaining to PARP inhibitor use to address several clinical issues, including strategies to optimize patient selection, clinical testing approaches, and potential application of PARP inhibitors in different lines of therapy. This activity will also investigate the mechanistic underpinnings of PARP inhibitor therapy, as well as which lessons from key PARP inhibitor studies may potentially be applied across different cancer types. Our panelists will conclude with a discussion of clinical cases and potential applications of PARP inhibitor therapy in different tumor types.

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Clovis Oncology, Inc.

CME Table of Contents

  • Introduction
  • Overview of PARP Inhibition and Synthetic Lethality
  • Medical Crossfire 1: Focus on Ovarian Cancer
  • Medical Crossfire 3: Focus on Prostate Cancer
  • Clinical Cases and Potential PARP Inhibitor Applications
  • Conclusion

Requirements for Successful Completion

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video” will be available for your reference.
  • In order to receive a CME certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME certificate upon completion of these steps.


Target Audience

This educational activity is directed toward medical oncologists, hematologists, pathologists, and fellows who treat patients with cancer. Nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of cancer may also participate.

Learning Objectives

At the conclusion of this activity, you should be better prepared to:

  • Determine key molecular underpinnings that provide the rationale for the targeting and investigation of PARP inhibition strategies for cancer treatment
  • Report pivotal and emerging evidence concerning the efficacy and safety of PARP inhibition strategies for the treatment of ovarian, breast, and prostate cancers
  • Place key trial evidence in the context of unmet clinical needs in the field and evolving treatment paradigms among solid tumors for which PARP inhibitor approaches have been investigated


Faculty, Staff, and Planners' Disclosures

Moderator

Mark E. Robson, MD
Attending Physician
Clinical Genetics and Breast Medicine Services
Clinic Director, Clinical Genetics Service
Memorial Sloan Kettering Cancer Center
New York, NY

Disclosure: Grant/Research Support: AztraZeneca, AbbVie, BioMarin; Consultant: McKesson, AstraZeneca NY

Faculty

Maurie Markman, MD
President, Medicine & Science
Cancer Treatment Centers of America
Clinical Professor of Medicine
Drexel University College of Medicine
Philadelphia, PA

Disclosure: Consultant: Celgene; Speaker’s Bureau: Clovis, AstraZeneca, Millennium, Merck, Celgene

Alicia K. Morgans, MD, MPH
Associate Professor of Medicine
Northwestern University Feinberg School of Medicine
Chicago, IL
 
 

Disclosure: Grant/Research Support: Prostate Cancer Foundation; Consultant: AstraZeneca, Janssen, Genentech

The staff of Physicians' Education Resource®, LLC have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing education purposes only, and is not meant to substitute for the independent medical judgment of a physician or nurse 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 of the companies that provided commercial support for this activity.

PER Pulse ™ Recap

PER Pulse Recap (1 of 3)

Overview of PARP Inhibition and Synthetic Lethality
 
This first of 3 PER Pulse Recaps focuses on the molecular underpinnings of poly (ADP-ribose) polymerase (PARP) inhibition therapy for multiple tumor types and the evolution of the concept of synthetic lethality. This concept has been studied extensively in preclinical and clinical studies, which addressed some of the key mechanisms that have been proposed to account for the efficacy of PARP inhibitors in influencing DNA damage repair in patients with breast, prostate, and ovarian cancers. Patients whose tumors have DNA damage repair defects may be particularly susceptible to PARP inhibitor therapy.1 As a component of this exploration of the roles of PARP inhibitors, Mark Robson, MD, discusses evolving models to account for the roles of PARP enzymes in DNA damage repair, as well as BRCA1 and BRCA2 mutations.
 
This discussion serves as a springboard for our panel discussion on the application of PARP inhibitor therapy in different tumor types. For additional commentary about these topics and others, visit www.gotoper.com to access more resources.
 
References
 
1. Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355(6330):1152-1158. doi: 10.1126/science.aam7344.


PER Pulse Recap (2 of 3)

Evolving Treatment Landscape for Breast, Ovarian, and Prostate Cancer
 
This second of 3 PER Pulse Recaps focuses on the evolving roles of poly (ADP-ribose) polymerase (PARP) inhibition in the treatment of patients with a variety of solid malignancies, including breast, ovarian, and prostate cancer. Given the increasing amount of clinical evidence pertaining to PARP inhibitor therapy in the treatment of different tumor types, it is important for clinicians to be able to understand the implications of this evidence for treatment paradigms.
 
In this Medical Crossfire®, Maurie Markman, MD; Alicia Morgans, MD; and Mark Robson, MD, review key studies of the use of PARP inhibitor therapy for different malignancies, discuss how this evidence is shaping clinical treatment options, and offer their perspectives on testing strategies and other options to optimize the potential application of PARP inhibitors. Dr. Markman begins the discussion with a review of the evolution of PARP inhibitors in ovarian cancer, including recent key studies in the maintenance setting.1-5 This is followed by Dr. Robson’s presentation of data from phase III studies of PARP inhibitors in the treatment of patients with breast cancer,6,7 as well as other intriguing studies that are currently in progress. Dr. Morgans presents landmark data regarding the use of PARP inhibition in prostate cancer8 and other studies whose findings may help to answer questions regarding which patients may benefit from this class of therapy. These presentations are balanced with a dynamic discussion of the implications of these data for practicing clinicians, as well as testing strategies that have been pursued as a means of optimizing PARP inhibitor use for different patient populations.
 
For additional commentary about these topics and others, visit www.gotoper.com to access more resources.
 
References
1. Pujade-Lauraine E, Ledermann JA, Selle F, et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2.
2. Mirza MR, Monk BJ, Herrstedt J, et al; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164.
3. Coleman RL, Oza AM, Lorusso D, et al; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6.
4. Kim G, Ison G, McKee AE, et al. FDA Approval Summary: olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy. Clin Cancer Res. 2015;21(19):4257-4261. doi: 10.1158/1078-0432.CCR-15-0887.
5. Balasubramaniam S, Beaver JA, Horton S, et al. FDA approval summary: rucaparib for the treatment of patients with deleterious BRCA mutation-associated advanced ovarian cancer. Clin Cancer Res. 2017;23(23):7165-7170. doi: 10.1158/1078-0432.CCR-17-1337.
6. Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523-533. doi: 10.1056/NEJMoa1706450.
7. Litton J, Rugo HS, Ettl J, et al. EMBRACA: a phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician’s choice of therapy in patients with advanced breast cancer and a germline BRCA mutation. Presented at: 2017 San Antonio Breast Cancer Symposium. December 8, 2017. Abstract GS6-07. abstracts2view.com/sabcs/view.php?nu=SABCS17L_1735.
8. Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373(18):1697-1708. doi: 10.1056/NEJMoa1506859.


PER Pulse Recap (3 of 3)

Clinical Considerations and Optimization of PARP Inhibitor Therapy
 
This third of 3 PER Pulse Recaps focuses on the clinical application of poly (ADP-ribose) polymerase inhibitor therapy, using cases to highlight and explore unresolved questions pertaining to the optimal application of this class of therapy. Dr. Markman, Dr. Morgans, and Dr. Robson address patients with progressive disease who have tried multiple lines of therapy, exploring the roles of different testing modalities in guiding therapy considerations, including options that look beyond germline BRCA mutations. This segment is intended to complement other segments of the Medical Crossfire® that address the implications of clinical evidence to date for PARP inhibitor therapy in multiple tumor types.
 
For additional commentary about these topics and others, visit www.gotoper.com to access more resources.








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