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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 2.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physicians' Education Resource®, LLC, is approved by the California Board of Registered Nursing, Provider #16669 for 2.0 Contact Hours.

Acknowledgement of Commercial Support

This activity is supported by educational grants from Clovis Oncology, Inc. and Myriad Genetics, Inc.

Community Practice Connections™: Redefining Ovarian Cancer Treatment Paradigms by Maximizing Therapeutic Outcomes with PARP Inhibitors

Release Date: September 29, 2017
Expiration Date: September 29, 2018
Media: Internet - based

 

Activity Overview

The treatment landscape for ovarian cancer has changed substantially with the introduction of poly (ADP-ribose) polymerase (PARP) inhibitor therapy. It is important for clinicians who treat patients with ovarian cancer to have a solid understanding of the mechanistic rationale for the use of these medications in order to optimize their therapeutic application. Other challenges associated with maximizing therapeutic outcomes with PARP inhibitor use include selection of optimal testing strategies to personalize care, management of treatment-related toxicities, and development of evidence-based sequencing and combination strategies.

This educational activity, featuring leading experts in the treatment of patients with ovarian cancer, was developed to help clinicians with the management of these challenges. Multiple topics pertaining to the use of PARP inhibitors in the treatment of ovarian cancers will be explored through a combination of didactic reviews of key data and short video interviews with the faculty addressing important clinical practice points.

Acknowledgement of Commercial Support

This activity is supported by educational grants from Clovis Oncology, Inc. and Myriad Genetics, Inc.

CME/CE Activity Table of Contents

  • Module A: Overview of Ovarian Cancer and Unmet Clinical Needs
  • Module B: Assessing Methods to Optimize Personalized Care in Ovarian Cancer
  • Module C: Current Methods and Future Directions to Optimize PARP Inhibition in Multiple Lines of Care
  • Module D: Management of Treatment-Related Toxicities Posttest

Instructions for This Activity and Receiving Credit

  • 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 files” will be available for your reference.
  • In order to receive a cme/ce 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/ce certificate upon completion of these steps.

Target Audience

This educational program is directed toward medical oncologists, surgical oncologists, and radiation oncologists interested in the treatment of ovarian cancers and other emerging tumor targets. Nurse practitioners, physician assistants, nurses, and other healthcare professionals involved in the treatment and management of patients with ovarian cancers may also participate.

Learning Objectives

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

  • Describe how PARP inhibition strategies have been applied to the management of recurrent ovarian cancer
  • Discuss how care can be personalized via the use of testing strategies in BRCA-mutated and non‒BRCA-mutated patient populations with ovarian cancer
  • Examine PARP inhibitor mechanisms in the context of treatment resistance and emerging role in the maintenance setting
  • Describe effective strategies to proactively plan for and manage treatment-related toxicities in the setting of ovarian cancer

Faculty, Staff, and Planners' Disclosures

Chair

Robert L. Coleman, MD, FACOG, FACS
Professor, Vice Chair of Clinical Research
Ann Rife Cox Chair in Gynecology
Department of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

Disclosure: Grant/ Research Support: Array BioPharma, AstraZeneca, Clovis Oncology, EMD Serono, Gradalis, Janssen, Merck; Consultant: AbbVie, Debiopharm, Genmab, ImmunoGen, Merrimack, Navigant Consulting, Perthera, Vaniam Group, LLC, Verastem; Speakers Bureau: AstraZeneca, BioAscend, Roche; Advisory Boards: AstraZeneca, Bayer Healthcare, Inc., Caris Life Sciences, Cerulean, Clovis Oncology, Gamamabs, Incyte, Janssen, Novocure, Pfizer, Precision Oncology, Roche, Tesaro

Faculty

Deborah K. Armstrong, MD
Professor of Oncology
Professor of Gynecology and Obstetrics
Johns Hopkins Kimmel Cancer Center
Baltimore, MD
 

Disclosure: Grant/ Research Support: AstraZeneca, Clovis; Consultant: Cue Biopharma

Michael J. Birrer, MD, PhD
Professor, Harvard Medical School
Director, Gynecologic Medical Oncology
Massachusetts General Hospital Cancer Center
Boston, MA
 

Disclosure: No relevant financial relationships with commercial interests to disclose.

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

Disclosure: Speakers Bureau: Clovis Oncology, Tesaro, AstraZeneca

The staff of PER® 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/CE activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME/CE 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/CE 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/CE activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician 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®.

PER Pulse™ Recap


1 of 3
PER Pulse™ Recap

Current Treatment Standards for Advanced Ovarian Cancer

Community Practice Connections™: Redefining Ovarian Cancer Treatment Paradigms by Maximizing Therapeutic Outcomes With PARP Inhibitors features a review of key data and evolving treatment paradigms highlighted at the live satellite symposium held at the 2017 American Society of Clinical Oncology annual conference. Interviews with distinguished ovarian cancer experts, including Robert L. Coleman, MD, FACOG, FACS; Deborah K. Armstrong, MD; Michael Birrer, MD; and Maurie Markman, MD, provide perspective on the clinical implications and patient management applications of emerging evidence and state-of-the-art approaches to the treatment of patients with advanced ovarian cancer. This first of 3 PER Pulse™ Recaps focuses on current treatment standards for advanced ovarian cancer.

  • Primary surgical management with the goal of maximal cytoreduction, followed by platinum-based combination chemotherapy, remains the standard of care for newly diagnosed ovarian cancer. Neoadjuvant chemotherapy may also be used.
  • A regimen incorporating a platinum agent and a taxane, administered for 6 to 8 cycles, is considered the standard for systemic therapy. Including bevacizumab, the anti-angiogenic agent, as part of the induction regimen and as a monotherapy for maintenance is supported by the improvement in progression-free survival observed in the phase III GOG 0218 and ICON7 trials.
  • For patients with recurrent, platinum-sensitive disease, treatment is typically an alternate platinum-based regimen, with or without bevacizumab. For platinum-resistant disease, options include single-agent therapy with a nonplatinum cytotoxic agent, such as docetaxel, etoposide, gemcitabine, liposomal doxorubicin, weekly paclitaxel, or topotecan. Bevacizumab and pazopanib have also demonstrated activity when added to chemotherapy in recurrent and refractory ovarian cancer.

For additional commentary about this topic and others, please visit www.gotoper.com.


2 of 3
PER Pulse™ Recap

PARP Inhibitors: Rationale, Current Evidence, and Future Directions

Community Practice Connections™: Redefining Ovarian Cancer Treatment Paradigms by Maximizing Therapeutic Outcomes With PARP Inhibitors features a review of key data and evolving treatment paradigms highlighted at the live satellite symposium held at the 2017 American Society of Clinical Oncology annual conference. Interviews with distinguished ovarian cancer experts, including Robert L. Coleman, MD, FACOG, FACS; Deborah K. Armstrong, MD; Michael Birrer, MD; and Maurie Markman, MD, provide perspective on the clinical implications and patient management applications of emerging evidence and state-of-the-art approaches to the treatment of patients with advanced ovarian cancer. This second of 3 PER Pulse™ Recaps focuses on the rationale for the use of poly (ADP-ribose) polymerase (PARP) inhibitors for advanced ovarian cancer, current evidence and indications, and future directions for investigation.

  • PARP inhibitors block the base excision single-strand DNA repair process, leading to the accumulation of double-strand breaks. In cells with an intact homologous recombination repair pathway, which targets double-strand breaks, PARP inhibition is nonlethal. However, in cells with a homologous recombination deficiency (HRD), inhibition of PARP causes catastrophic DNA damage, resulting in cell death. This concept known as synthetic lethality.
  • Mutation and silencing of the BRCA1/2 genes are the most common mechanisms that lead to HRD, but dysregulation of other genes involved in the double-strand DNA repair process may also confer sensitivity to PARP inhibitors. Several molecular assays have been developed to identify BRCA1/2 wild-type cancers that also demonstrate HRD.
  • Three PARP inhibitors have now received approval from the US Food and Drug Administration for use in advanced ovarian cancer.
    • Olaparib received accelerated approval for germline BRCA1/2-mutated advanced ovarian cancer previously treated with ≥3 lines of chemotherapy, based on results of a phase II trial demonstrating a 34% response rate and 40% stable disease rate in patients with platinum-resistant disease. More recently, the indication was expanded to include its use as a single-agent maintenance therapy for patients responding to a platinum-based regimen based on the significant extension of progression-free survival (PFS) observed in the phase III SOLO-2 trial.
    • Rucaparib received accelerated approval for the treatment of advanced ovarian cancer with either a germline or somatic BRCA mutation following ≥2 prior chemotherapies. Approval was based on the activity observed in the subgroup of patients with BRCA-mutant, recurrent, platinum-sensitive, high-grade ovarian cancers in the phase II ARIEL-2 study.
    • Niraparib is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. Approval was based on results from the phase III NOVA trial in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer, which demonstrated a significant improvement in median PFS with niraparib maintenance therapy compared with placebo.
  • Future directions include investigating PARP inhibitors in the upfront setting for newly diagnosed ovarian cancer. PARP inhibitors are also being evaluated in combination with other targeted agents, such as anti-angiogenic agents and immune checkpoint inhibitors.

For additional commentary about this topic and others, please visit www.gotoper.com.


3 of 3
PER Pulse™ Recap

Managing PARP Inhibitor-Associated Toxicities

Community Practice Connections™: Redefining Ovarian Cancer Treatment Paradigms by Maximizing Therapeutic Outcomes With PARP Inhibitors features a review of key data and evolving treatment paradigms highlighted at the live satellite symposium held at the 2017 American Society of Clinical Oncology annual conference. Interviews with distinguished ovarian cancer experts, including Robert L. Coleman, MD, FACOG, FACS; Deborah K. Armstrong, MD; Michael Birrer, MD; and Maurie Markman, MD, provide perspective on the clinical implications and patient management applications of emerging evidence and state-of-the-art approaches to the treatment of patients with advanced ovarian cancer. This third of 3 PER Pulse™ Recaps focuses on the management of side effects associated with the use of poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced ovarian cancer.

For additional commentary about this topic and others, please visit www.gotoper.com.

  • PARP inhibitors are generally well tolerated, even in heavily pretreated patients, and grade 4 adverse events are rare.
  • The most common hematologic toxicities associated with the available PARP inhibitors are anemia, thrombocytopenia, and neutropenia. Regular monitoring of blood counts is necessary and transfusions may be used as needed.
  • Gastrointestinal adverse events, such as nausea, vomiting, diarrhea, and constipation also appear to be a class effect. Antiemetics, antidiarrheals, and laxatives can be useful in preventing and managing these toxicities.
  • One rare but serious potential side effect that appears to be associated with all of the available PARP inhibitors is the increased risk of development of myelodysplastic syndrome or acute myelogenous leukemia, with rates of 1.1% to 1.4% observed in clinical trials to date. If hematologic toxicities do not resolve promptly (within 4 weeks) after discontinuation of PARP inhibitor therapy, a hematologic work-up should be performed.






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